Transcriptional Regulation of Gene Expression in C. elegans

Abstract

Protein coding gene sequences are converted to mRNA by the highly regulated process of transcription. The precise temporal and spatial control of transcription for many genes is an essential part of development in metazoans. Thus, understanding the molecular mechanisms underlying transcriptional control is essential to understanding cell fate determination during embryogenesis, post-embryonic development, many environmental interactions, and disease-related processes. Studies of transcriptional regulation in C. elegans exploit its genomic simplicity and physical characteristics to define regulatory events with single cell and minute time scale resolution. When combined with the genetics of the system, C. elegans offers a unique and powerful vantage point from which to study how chromatin-associated protein and their modifications interact with transcription factors and their binding sites to yield precise control of gene expression through transcriptional regulation.

1. Overview

Every aspect of cellular function depends on the gene products expressed in that cell. The mechanisms regulating the expression of these gene products are diverse, and they can affect each of the steps necessary to make and maintain a steady state level of functional RNA or protein. These mechanisms include those controlling RNA synthesis, processing, and stability, and, in the case of protein coding genes, protein translation, modification and degradation. Here we focus on the regulation of RNA transcription in C. elegans. Transcription is a necessary first step in gene expression, and transcriptional regulation plays a central role in organismal development and evolution (Levine and Tjian, 2003; PMID 12853946; Chen and Rajewsky, 2007; PMID 17230196). Indeed, the number of specific proteins involved in transcription and its regulation increases with increasing organismal complexity (Vogel and Chothia, 2006; PMID 16733546).

Many of the general characteristics that make C. elegans an excellent model system (invariant lineage, simple anatomy, effectiveness of RNAi, etc) also make it an excellent system to study transcriptional regulation. However, two specific characteristics uniquely facilitate transcriptional regulation studies in the worm. First, C. elegans is transparent throughout its entire life cycle making it an ideal system to use fluorescent protein reporter genes to monitor gene expression in live animals with single cell resolution. Second, the relatively compact size of the C. elegans genome facilitates identification of cis-acting transcriptional regulatory elements (CREs) controlling gene expression. Examples of the success of studying transcriptional control in C. elegans are reviewed in WormBook and elsewhere, and they include the elucidation of the transcriptional cascade controlling specification and differentiation of the gut, nervous system, and pharynx (Hobert, 2010; PMID 20891032; Mango, 2007; PMID 18050503; McGhee, 2007; PMID 18050495). These two physical characteristics are augmented by facile forward and reverse genetics in the C. elegans system. Mutations affecting numerous transcription factors and even CREs have provided important insights into the transcriptional control of cell fate decisions during development, such as specifying which cells undergo apoptosis (Conradt and Xue, 2005; PMID 18061982), while characterization of dosage compensation (Meyer, 2010; PMID 20381335) and the synMuv mutants (Fay and Yochem, 2007; PMID 17434473) have broadened our general understanding gene regulation at the chromatin level. These advantages have consistently provided novel mechanistic insights into the transcription regulation of gene expression.

This chapter provides an overview of RNA Pol II transcription in C. elegans, focusing on what we have learned to date about gene expression in the somatic cells of the animal. Although much of the content of this review is also applicable to germline transcription, readers interested in germline gene expression are encouraged to see WormBook chapters Germline Genomics and Germline Chromatin, as important differences exist in the mechanisms controlling expression in these two tissue types. This chapter takes a broad strokes approach to somatic transcription while providing references to serve as entry points for those wanting to explore particular topics in more detail. A brief introduction into the basics of gene organization and regulation sets the stage for those unfamiliar with C. elegans gene expression. This is followed by a discussion of transcription factor function, and the chapter ends with the known roles for chromatin in C. elegans gene regulation. Although some basic information may duplicate that found in previous reviews of transcriptional regulation (Blackwell and Walker, 2006; PMID 18050436; Gaudet and McGhee, 2010; PMID 20175193; Krause, 1995; PMID 8531739; McGhee and Krause, 1997; Okkema and Krause, 2005; PMID 18050428; Van Nostrand and Kim, 2011; PMID 21963133), this review aims to augment rather than supersede these alternate overviews as each has valuable information and a unique perspective on transcriptional regulation.

2. RNA Polymerase II and Associated Factors

The regulation of RNA Polymerase II (Pol II)-mediated transcription in C. elegans can be described as typical for eucaryotes. Pol II appears to act in concert with TATA Binding Protein (TBP) and TBP-Associated Factors (TAFs) at the core promoter of protein coding genes (Dantonel et al., 2000; PMID 11030350; Kaltenbach et al., 2000; PMID 11030349; Lichtsteiner and Tjian, 1993; PMID 8415761; Walker et al., 2004; PMID 14726532)(see also WormBook chapter Transcripton Mechanisms). As in other eucaryotyes, the large subunit of Pol II of C. elegans, encoded by the ama-1 gene (Bird and Riddle, 1989; PMID 2586513), has an extended C-terminal domain (CTD) that likely serves as a binding site for protein complexes involved in co-transcriptional mRNA processing and histone modification (Figure 1; from Phatnani and Greenleaf, 2006; PMID 17079683). Active Pol II is phosphorylated on the CTD at serine 2 and 5 (Ser2P or Ser5P) of the conserved heptad repeat (YSTPSPS) and its variants, as it is in other eucaryotes (Seydoux and Dunn, 1997; PMID 9187145; Wallenfang and Seydoux, 2002; PMID 11960010; Zhang et al., 2003; PMID 12651893). The levels of Ser2P increase while the Ser5P level decrease with transcriptional elongation in eucaryotes (Buratowski, 2009; PMID 19941815) and there is some evidence for the same in C. elegans (Garrido-Lecca and Blumenthal, 2010; PMID 20498277). Interestingly, many of the antibodies used to distinguish these Pol II isoforms based on heptad repeat phosphorylation epitopes yield very similar patterns by chromatin immunoprecipitation (ChIP) in C. elegans (Baugh et al., 2009; PMID 19251593; Pferdehirt et al., 2011; PMID 21363964). The functions of many of the other core transcription factors are similarly conserved with one of the only major differences being the absence of the negative elongation factor NELF (reviewed in (Blackwell and Walker, 2006; PMID 18050436)).

Figure 1. A hypothetical RNAPII elongation megacomplex.

RNAPII (including the extended CTD with SerPO4 knobs) is purple; the globular and CTD portions are drawn approximately to scale for mammalian RNAPII. Orange DNA is wrapped around yellow nucleosomal histones; nucleosomes modified by Set2 are shaded darker. The nascent RNA transcript is green. Yeast names are used for PCAPs (e.g., Phatnani and Greenleaf, 2006; PMID 17079683), not all of which are shown. (CBC) cap-binding complex; (CRF) chromatin remodeling factor; (XF) processing/export factor. (Used with permission Phatnani and Greenleaf, 2006; PMID 17079683)

3. C. elegans Gene Organization and Regulation

Transcriptional regulation results from a complex organization of cis-acting sequences that serve as binding sites for a multitude of trans-acting factors that together determine if a gene will be active or silent. In higher eucaryotes, these cis-acting sequences are typically clustered into discrete functional modules, including the core promoter, extended proximal and downstream promoter regions, positive and negative enhancers, and insulators as diagramed in Figure 2 (Levine and Tjian, 2003; PMID 12853946).

Figure 2. Metazoan regulatory modules controlling transcription.

Shown is a diagram of a typical metazoan gene illustrating the complex interactions among cis-acting modules and trans-acting factors regulating gene expression. Note that both positive and negative control regions are interspersed with promoter modules, all of which can be further influenced by distal regions regulating chromatin configuration, such as insulators. (Used with permission Levine and Tjian, 2003; PMID 12853946)

3.1 Proximal Control Regions

The majority of protein coding genes in C. elegans are within relatively gene-dense regions of the genome. Consequently, cis-acting regulatory regions are usually close to the coding region. In fact, a good rule of thumb for C. elegans is that the minimal set of cis-acting sequences sufficient to regulate proper gene expression is found within 2 kb upstream of the translational start codon. Often, another gene is present on the same or opposite strand and located less than 2 kb upstream of the gene of interest. Generally in these cases, one assumes the minimal promoter is restricted to the non-coding, intergenic region. There are notable exceptions to this compact view of cis-acting sequences. For example, egl-1 expression is controlled, in part, by elements located both upstream and more than 4 kb downstream of the coding region (Thellmann et al., 2003; PMID 12874127; Winn et al., 2011; PMID 21596899). For lin-39, proper reporter gene expression required inclusion of ~30 kb of genomic DNA that extends long distances upstream and downstream of the protein coding region (Wagmaister et al., 2006; PMID 16782085). Clearly C. elegans genes can have complex and distant control regions so the 2 kb rule of thumb should not be mistaken for dogma.

It is important to remember that the minimal promoter region is not synonymous with the natural promoter. The natural promoter may span a much larger region due to redundancy in the function of regulatory elements that ensure proper and robust regulation of the endogenous gene. One common site of additional control elements is within the introns. Most C. elegans introns are small (e.g. <100 bp; see WormBook chapter Overview of Gene Structure) and are thus unlikely to contain elements controlling expression. However, introns larger than several hundred base pairs do often have such elements (e.g., (Nam et al., 2002; PMID 11756550; Okkema et al., 1993; PMID 8244003; Kostrouchova et al., 1998; PMID 9521900)). Therefore, intron size can provide a clue in searching for transcriptional control sequences.

3.2 Distal Control Regions

The relatively compact C. elegans genome may also underlie the apparent absence of long-range control mechanisms for gene regulation that are common to other metazoa. For example, CTCF in vertebrates and flies plays a key role in long-range chromatin organization and can block enhancer-stimulated gene expression, thus functioning as an insulator as shown in Figure 2 (Wallace and Felsenfeld, 2007; PMID 17913488). To date, there is no evidence for an ortholog or functional equivalent of CTCF in C. elegans. Thus, both the local and global organization of genes in C. elegans appears to be relatively simple in comparison with other metazoans, presumably simplifying our understanding of transcriptional regulation.

3.3 Transcriptional Initiation and Trans-Splicing

Another unusual aspect of the C. elegans system to note when considering transcriptional regulation is the occurrence of trans-splicing, a process that replaces the initial transcript 5’ untranslated region (5’ UTR) with a 22 nucleotide leader sequence (SL1) for the majority of Pol II messages ((Allen et al., 2011; PMID 21177958; Krause and Hirsh, 1987; PMID 3581169), see WormBook chapter Trans-splicing and Operons). Therefore, mapping the 5’ start site of the mature mRNA often only reveals the site of trans-splicing, not transcriptional initiation, complicating analyses that are commonplace in other systems. The ability to trans-splice messages also provides a processing mechanism for polycistronic messages, or operons, in C. elegans ((Spieth et al., 1993; PMID 8098272), reviewed in (Blumenthal, 2005; PMID 18050426)). The sequence of the spliced leader present on the mature message distinguishes the first gene of an operon (no SL or SL1 trans-spliced) versus internal messages of the operon (SL2 trans-spliced). Typically, the tightly clustered genes of an operon are co-regulated due to their polycistronic nature, although the use of different promoters upstream and within operons can result in independent transcriptional regulation of one or more of the mRNAs (Allen et al., 2011; PMID 21177958; Blumenthal, 2005; PMID 18050426; Huang et al., 2007; PMID 17712020; Yin et al., 2010; PMID 20565799; Morton and Blumenthal, 2011; PMID 21156961).

3.4 Core Promoter Elements

Ironically, the study of common sequences among messages trans-spliced provided the first systematic information on common promoter sequences (Graber et al., 2007; PMID 17630324), revealing the presence of a consensus Kozak sequence regulating translational initiation (Kozak, 1981; PMID 7301588). A more recent study of promoter sequences has extended this analysis to define the core promoter sequence elements typically present in C. elegans (Grishkevich et al., 2011; PMID 21367940). The five elements commonly observed are an Sp1 like site (CNCCGCCC), T-blocks that correlate with nucleosome eviction and gene expression levels (TTTT[N/T]), TATA box (GTATA[TA][TA]AG), trans-splicing site (TTnCAG), and Kozak site that includes the translation initiation codon ([CA]AA[CA]ATG) ((Grishkevich et al., 2011; PMID 21367940) (Figure 3). The sensitivity and depth of coverage of next generation sequencing based techniques will allow fine scale mapping of primary transcript start sites of outron-containing genes in the near future, aiding in our understanding of transcriptional initiation and requisite regulatory sequences in the near future.

Figure 3. Core promoter motif composition among Caenorhabditis promoters.

Motif composition of the Caenorhabditis core promoter. (A) Five conserved motifs in each of the five examined Caenorhabditis species are shown as sequence logos. (*) In contrast to all other motifs that were found in the initial search, the Caenorhabditis japonica TATA box motif was detected only in sequences whose orthologs contained the “TATA” motif. (B) Distribution of motifs relative to the translational start codon. The gray box in each plot corresponds to the core promoter. The area under the curve is the total frequency of occurrence within the core promoter region with the line indicating the frequency at each position as indicated by the scale to the left. The C. japonica SL1 motif was normalized to the length of the other species. (C) Frequency table for each sequence motif. (Figure and data used with permission Grishkevich et al., 2011; PMID 21367940)

4. Promoter Complexity

Two general types of promoter organization have been described in C. elegans; simple and complex. A simple promoter is defined here as one in which the cis-acting control elements necessary for proper expression are confined to a small region (a few hundreds of bp) of the genome. Housekeeping genes expressed in all tissues are good candidates for regulation by simple promoters, although few housekeeping genes in C. elegans have been well characterized. Among the best-characterized simple promoters are those of the hsp-16 family of genes. This family consists of pairs of divergently transcribed genes with promoter regions sufficient for heat-regulated expression contained within the short (~350 bp) intergenic regions (Jones et al., 1986; PMID 3017958; Russnak and Candido, 1985; PMID 4033652; Stringham et al., 1992; PMID 1550963). Despite these compact promoters, distinct tissue expression patterns are induced from different hsp-16 promoters (Stringham et al., 1992; PMID 1550963), suggesting the presence of multiple regulatory sites within these simple promoters. Another excellent example of simple promoters are in the vitellogenin (vit) genes, which exhibit stage-, tissue- and sex-specific expression controlled, in the case of vit-2, by a 247 bp promoter (MacMorris et al., 1992; PMID 1549118; MacMorris et al., 1994; PMID 8264616). vit-2 promoter activity depends on GATA-factor binding sites and a novel VPE2 site (TGTCAAT) conserved in vit gene promoters in C. elegans and C. briggsae (Spieth et al., 1985; PMID 4022780; Zucker-Aprison and Blumenthal, 1989; PMID 2504925). Certain cell cycle promoters have also been shown to be remarkably simple. Analysis of several genes expressed only in proliferative cells and encoding G1 phase regulators (e.g. cyclin D) revealed that proper regulation required as little as 67 base pairs from the promoter (Brodigan et al., 2003; PMID 12606285; Park and Krause, 1999; PMID 10518501).

In contrast to the simple promoters, complex promoters contain dispersed regulatory elements in which the overall pattern of gene expression is the result of the composite action of several dispersed elements, each influencing or contributing to the overall expression pattern. Complex promoters are often associated with regulatory genes controlling a key developmental decision. For example, the piecemeal organization of the regulatory regions for hlh-1 and lin-26 reflect a need for these promoters to integrate a variety of different cell lineage inputs to control proper cell fate specification in the correct cells at the appropriate time during development (reviewed in (Okkema and Krause, 2005; PMID 18050428)).

5. Transcription Factors

Proper spatial and temporal regulation of gene expression depends on the binding of transcription factors to specific gene cis-regulatory sequences (Levine and Tjian, 2003; PMID 12853946). A variety of C. elegans transcription factors are well characterized and have important developmental roles; however it remains a challenge to accurately catalog all the transcription factors encoded in the C. elegans genome. Automated searches for gene ontology terms associated with transcriptional regulation can result in inclusion of false positive hits for transcription factors (Reece-Hoyes et al., 2005; PMID 16420670; Vaquerizas et al., 2009; PMID 19274049). In some cases there is ambiguity as to whether a particular domain defines the protein as a DNA-binding factor. For example, various types of zinc finger domains can bind DNA but can also serve other functions, including RNA binding and protein-protein interactions (Gamsjaeger et al., 2007; PMID 17210253; Matthews and Sunde, 2002; PMID 12665246). Likewise, for factors that modify chromatin or participate in a transcription complex, the definition of a transcription factor often lies in the eyes of the investigator. Finally, gene annotations change as new information regarding gene structure is obtained and new classes of DNA-binding transcription factors are discovered. Thus any list of transcription factors must be manually curated and periodically updated to include the latest gene annotations.

5.1 Transcription Factor Resources

Several groups have produced excellent catalogs of transcription factors in C. elegans using predictions based on gene ontology terms associated with transcription and DNA-binding domain assignments, followed by manual curation, to produce lists of transcription factor genes containing between 934 and 988 genes (Barrasa et al., 2007; PMID 17233892; Haerty et al., 2008; PMID 18752680; Reece-Hoyes et al., 2005; PMID 16420670; Wilson et al., 2008; PMID 18073188; Reece-Hoyes et al., 2011; PMID 22037705). While these lists are largely overlapping, they are not identical, so it may be useful to scan each of these lists for your favorite genes (http://edgedb.umassmed.edu/; http://www.macwormlab.net/ntfdb/index.php http://dbd.mrc-lmb.cam.ac.uk/DBD/index.cgi?Home).

The most recent catalog is wTF2.2 (Reece-Hoyes et al., 2011; PMID 22037705), and we have updated and annotated this list with current gene names (Table 1). Fifty-three transcription factor genes were removed from wTF2.2 either due to reannotation of the genome, or because there was only weak evidence that motifs in these genes encoded DNA-binding domains [e.g., ZF - A20 (IPR002653), ZF - CCCH (IPR000571), ZF – DHHC (IPR001594), and ZF – MIZ(IPR004181)]. We have also added forty transcription factor genes that had been identified as DNA binding proteins in large scale yeast 1-hybrid screens (Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705), or based on information from other transcription factor catalogs (Haerty et al., 2008; PMID 18752680; Wilson et al., 2008; PMID 18073188). Our catalog contains 924 transcription factor genes, which is ~4.6% of all protein coding genes (WS220). This number is slightly less than the frequency of transcription factor genes in the human genome (~6% of the protein coding genes) (Vaquerizas et al., 2009; PMID 19274049). Commercially available feeding RNAi clones targeting many of these genes are available (Table 1), facilitating functional analysis of C. elegans transcription factors.

Gene WB ID	Sequence Name (Gene)	Gene Public Name	DNA binding domain	Closest Human Protein ID	HUGO ID	Commercially available feeding RNAi clone
WBGene00019424	K06A1.1	aptf-1	AP-2	ENSP00000263543	TFAP2E	1, 2
WBGene00009202	F28C6.1	F28C6.1	AP-2			1, 2
WBGene00009203	F28C6.2	F28C6.2	AP-2			1, 2
WBGene00013383	Y62E10A.17	Y62E10A.17	AP-2			1, 2
WBGene00000476	T23D8.8	cfi-1	ARID/BRIGHT	ENSP00000263620	ARID3A	1, 2
WBGene00002717	C01G8.9	let-526	ARID/BRIGHT	ENSP00000337170	ARID1A	1, 2
WBGene00004319	ZK593.4	rbr-2	ARID/BRIGHT	ENSP00000235790	JARID1B	1, 2
WBGene00044689	Y108G3AL.7	Y108G3AL.7	ARID/BRIGHT
WBGene00019217	H20J04.2	athp-2	AT Hook	ENSP00000353458	BAZ1A	1
WBGene00015477	C05D10.1	attf-4	AT Hook			1, 2
WBGene00020214	T04G9.1	attf-5	AT Hook			1, 2
WBGene00007094	B0019.2	B0019.2	AT Hook			1
WBGene00045419	R07B5.9	lsy-12	AT Hook			1
WBGene00009180	F26H11.2	nurf-1	AT Hook	ENSP00000334351		1
WBGene00007761	C27B7.4	rad-26	AT Hook	ENSP00000296477		1
WBGene00011964	T23G5.6	saeg-2	AT Hook	ENSP00000217439	DNTTIP1	1, 2
WBGene00011729	T12D8.1	set-16	AT Hook	ENSP00000301067	MLL2	1
WBGene00020408	T10D4.6	T10D4.6	AT Hook			1, 2
WBGene00012715	Y39E4B.2	Y39E4B.2	AT Hook			2
WBGene00017482	F15E6.1	set-9	AT Hook x1	ENSP00000257745		1
WBGene00008081	C44B9.4	athp-1	AT Hook x2			1, 2
WBGene00012474	Y18D10A.1	attf-6	AT Hook x2	ENSP00000251819	PRG4	1
WBGene00003210	C38D4.3	mel-28	AT Hook x2	ENSP00000311997	NEFH	1
WBGene00001514	C05D2.5	xnd-1	AT Hook x2			1
WBGene00023497	ZK662.4	lin-15B	AT Hook x2, ZF - THAP
WBGene00017317	F09G2.9	attf-2	AT Hook x3			1, 2
WBGene00017423	F13C5.2	F13C5.2	AT Hook x3			1, 2
WBGene00001976	T05A7.4	hmg-11	AT Hook x3			1, 2
WBGene00004157	W03D2.1	pqn-75	AT Hook x3			1, 2
WBGene00013799	Y116A8C.22	athp-3	AT Hook x5			1, 2
WBGene00001977	Y17G7A.1	hmg-12	AT Hook x7			1, 2
WBGene00002169	F37A4.8	isw-1	AT Hook, MYB x2	ENSP00000218157	SMARCA1	1, 2
WBGene00008092	C44F1.2	gmeb-3	AT Hook, SAND	ENSP00000355186		1, 2
WBGene00007732	C25G4.4	gmeb-4	AT Hook, SAND	ENSP00000294409	GMEB1	1, 2
WBGene00000095	C25A1.11	aha-1	bHLH	ENSP00000307479	ARNT2	1, 2
WBGene00000096	C41G7.5	ahr-1	bHLH	ENSP00000242057	AHR	1, 2
WBGene00000521	C15C8.2	cky-1	bHLH	ENSP00000311196		2
WBGene00000561	C34E10.7	cnd-1	bHLH	ENSP00000295108	NEUROD1	1, 2
WBGene00001851	F38A6.3	hif-1	bHLH	ENSP00000323326		1
WBGene00001948	B0304.1	hlh-1	bHLH	ENSP00000228641	MYF6	1, 2
WBGene00001954	ZK682.4	hlh-10	bHLH	ENSP00000237316	TCF21	1, 2
WBGene00001955	F58A4.7	hlh-11	bHLH	ENSP00000204517	TFAP4	1, 2
WBGene00001956	C28C12.8	hlh-12	bHLH			1
WBGene00001957	F48D6.3	hlh-13	bHLH	ENSP00000306982	PTF1A	1
WBGene00001958	C18A3.8	hlh-14	bHLH	ENSP00000302216	ATOH1	1
WBGene00001959	C43H6.8	hlh-15	bHLH	ENSP00000302189	NHLH1	1, 2
WBGene00001960	DY3.3	hlh-16	bHLH	ENSP00000245673	BHLHB4	1
WBGene00001961	F38C2.2	hlh-17	bHLH	ENSP00000318799	BHLHB5
WBGene00001962	F57C12.3	hlh-19	bHLH			1, 2
WBGene00001949	M05B5.5	hlh-2	bHLH	ENSP00000262965	TCF3	1, 2
WBGene00001964	C17C3.7	hlh-25	bHLH			1
WBGene00001966	C17C3.10	hlh-27	bHLH			1
WBGene00001950	T24B8.6	hlh-3	bHLH	ENSP00000266744	ASCL1	1
WBGene00020930	W02C12.3	hlh-30	bHLH	ENSP00000324246		1, 2
WBGene00009540	F38C2.8	hlh-31	bHLH	ENSP00000318799	BHLHB5	1
WBGene00013665	Y105C5B.29	hlh-32	bHLH	ENSP00000318799	BHLHB5
WBGene00021446	Y39A3CR.6	hlh-33	bHLH			1, 2
WBGene00011327	T01D3.2	hlh-34	bHLH	ENSP00000348460	NPAS3	1, 2
WBGene00001951	T05G5.2	hlh-4	bHLH			1, 2
WBGene00001952	T15H9.3	hlh-6	bHLH	ENSP00000318846	ASCL3	1, 2
WBGene00001953	C02B8.4	hlh-8	bHLH	ENSP00000242261	TWIST1	1, 2
WBGene00001981	C44C10.8	hnd-1	bHLH			1, 2
WBGene00003008	Y54G2A.1	lin-22	bHLH	ENSP00000232424	HES1
WBGene00003018	T14F9.5	lin-32	bHLH	ENSP00000302216	ATOH1	1, 2
WBGene00003163	R03E9.1	mdl-1	bHLH	ENSP00000331152		1, 2
WBGene00003378	T20B12.6	mml-1	bHLH	ENSP00000312834		1, 2
WBGene00003509	T19B10.11	mxl-1	bHLH	ENSP00000351490	MAX	1, 2
WBGene00003510	F40G9.11	mxl-2	bHLH	ENSP00000246912	MLX	1, 2
WBGene00003511	F46G10.6	mxl-3	bHLH	ENSP00000351490	MAX	1, 2
WBGene00003595	Y69A2AR.29	ngn-1	bHLH	ENSP00000295108	NEUROD1	1
WBGene00004735	Y47D3B.7	sbp-1	bHLH	ENSP00000354476	SREBF2	1, 2
WBGene00001965	C17C3.8	hlh-26	bHLH - 2 domains			1, 2
WBGene00001967	F31A3.2	hlh-28	bHLH - 2 domains			1
WBGene00001968	F31A3.4	hlh-29	bHLH - 2 domains			1, 2
WBGene00004334	T01E8.2	ref-1	bHLH - 2 domains			1
WBGene00000221	T04C10.4	atf-5	bZIP			1, 2
WBGene00000222	F45E6.2	atf-6	bZIP	ENSP00000263291	ATF6	1, 2
WBGene00000223	C07G2.2	atf-7	bZIP	ENSP00000344614		2
WBGene00017535	F17A9.3	atf-8	bZIP	ENSP00000222122	DBP	2
WBGene00013878	ZC376.7	atfs-1	bZIP			2
WBGene00016754	C48E7.11	C48E7.11	bZIP	ENSP00000284000	CEBPG
WBGene00016997	D1005.3	cebp-1	bZIP	ENSP00000352916		1, 2
WBGene00000469	ZK909.4	ces-2	bZIP	ENSP00000222122	DBP	1, 2
WBGene00000793	Y41C4A.4	crh-1	bZIP	ENSP00000236996	CREB1	2
WBGene00016162	C27D6.4	crh-2	bZIP	ENSP00000329140	CREB3L2	1
WBGene00001345	F29G9.4	fos-1	bZIP	ENSP00000295499	ATF2	1, 2
WBGene00012005	T24H10.7	jun-1	bZIP			1, 2
WBGene00002783	F57B10.1	let-607	bZIP	ENSP00000078445		1, 2
WBGene00022500	ZC8.4	lfi-1	bZIP	ENSP00000072205	CROCC	1, 2
WBGene00003059	C48E7.3	lpd-2	bZIP	ENSP00000352360		1
WBGene00077521	F45H11.6	maf-1	bZIP
WBGene00003233	F45H11.4	mgl-2	bZIP	ENSP00000282753	GRM1	1
WBGene00004804	T19E7.2	skn-1	bZIP	ENSP00000234401	NFE2L2	1, 2
WBGene00020961	W02H5.7	sknr-1	bZIP	ENSP00000234401	NFE2L2	1
WBGene00006959	R74.3	xbp-1	bZIP	ENSP00000216037	XBP1	1, 2
WBGene00006986	Y75B8A.35	zip-1	bZIP			2
WBGene00012101	T27F2.4	zip-10	bZIP			1, 2
WBGene00021082	W08E12.1	zip-11	bZIP			1, 2
WBGene00013560	Y75B8A.29	zip-12	bZIP			1, 2
WBGene00019327	K02F3.4	zip-2	bZIP			1, 2
WBGene00012330	W07G1.3	zip-3	bZIP	ENSP00000307356	ATF5
WBGene00021552	Y44E3B.1	zip-4	bZIP	ENSP00000305422	CEBPB	1
WBGene00007932	C34D1.5	zip-5	bZIP			1, 2
WBGene00011130	R07H5.10	zip-6	bZIP	ENSP00000350359	CREB5	1
WBGene00013100	Y51H4A.4	zip-7	bZIP	ENSP00000222122	DBP	1, 2
WBGene00017755	F23F12.9	zip-8	bZIP			1, 2
WBGene00077761	F17C11.17	zip-9	bZIP
WBGene00000220	K08F8.2	atf-2	bZIP - 2 domains	ENSP00000297689	NFIL3	1, 2
WBGene00009584	F40F9.7	drap-1	CBF	ENSP00000307850	DRAP1
WBGene00001092	F53A2.5	dro-1	CBF	ENSP00000236164	DR1	1, 2
WBGene00009084	F23B12.7	F23B12.7	CBF	ENSP00000234170	CEBPZ	1, 2
WBGene00011614	T08D10.1	nfya-1	CBF	ENSP00000229418		1, 2
WBGene00043056	Y53H1A.5	nfya-2	CBF	ENSP00000229418		1
WBGene00021132	W10D9.4	nfyb-1	CBF	ENSP00000240055	NFYB	2
WBGene00017742	F23F1.1	nfyc-1	CBF	ENSP00000330989		1
WBGene00020823	T26A5.8	T26A5.8	CBF	ENSP00000277334	POLE3	1, 2
WBGene00013150	Y53F4B.3	Y53F4B.3	CBF	ENSP00000233699	POLE4	1, 2
WBGene00000472	F33A8.3	cey-1	COLD BOX	ENSP00000228251	CSDA	1, 2
WBGene00000473	F46F11.2	cey-2	COLD BOX	ENSP00000163282	NSEP1	1, 2
WBGene00000474	M01E11.5	cey-3	COLD BOX	ENSP00000163282	NSEP1	1, 2
WBGene00000475	Y39A1C.3	cey-4	COLD BOX	ENSP00000279550		1
WBGene00003014	F02E9.2	lin-28	COLD BOX	ENSP00000344401		2
WBGene00001707	Y48G8AR.1	grh-1	CP2	ENSP00000251808		1
WBGene00009672	F43G9.12	F43G9.12	GC-rich DNA-binding domain			1, 2
WBGene00007412	C07E3.1	stip-1	GC-rich DNA-binding domain
WBGene00045215	C02F12.10	C02F12.10	HD			1
WBGene00020485	T13C5.4	ceh-54	HD	ENSP00000221996	CRX	1, 2
WBGene00007416	C07E3.5	ceh-57	HD			1
WBGene00000432	C34C6.8	ceh-7	HD	ENSP00000234392	VAX2	1
WBGene00013876	ZC376.4	ceh-74	HD			1, 2
WBGene00007749	C26E1.3	ceh-79	HD			1, 2
WBGene00018434	F45C12.3	ceh-81	HD			1
WBGene00018433	F45C12.2	ceh-82	HD	ENSP00000311467		1, 2
WBGene00019137	F59H6.6	ceh-85	HD			1
WBGene00018355	F42G2.6	ceh-86	HD			1, 2
WBGene00018022	F34D6.2	ceh-87	HD
WBGene00010995	R03E1.4	ceh-90	HD
WBGene00013425	Y66A7A.5	ceh-91	HD - 2 domains			1, 2
WBGene00019864	R04A9.5	ceh-93	HD - 2 domains
WBGene00022861	ZK1193.5	dve-1	HD - 2 domains			1
WBGene00000444	T26C11.6	ceh-21	HD - CUT			1, 2
WBGene00000459	F22D3.1	ceh-38	HD - CUT			2
WBGene00000460	T26C11.7	ceh-39	HD - CUT			2
WBGene00000462	T26C11.5	ceh-41	HD - CUT			1, 2
WBGene00000464	Y54F10AM.4	ceh-44	HD - CUT	ENSP00000342189
WBGene00015934	C17H12.9	ceh-48	HD - CUT	ENSP00000262095	ONECUT2	1, 2
WBGene00017538	F17A9.6	ceh-49	HD - CUT			1, 2
WBGene00044508	C18F3.4	nsy-7	HD - distant
WBGene00018786	F54A5.1	hmbx-1	HD - HNF	ENSP00000347371		1, 2
WBGene00000436	F33D11.4	ceh-12	HD - HOX	ENSP00000252971	HLXB9	2
WBGene00000437	R13A5.5	ceh-13	HD - HOX	ENSP00000355140	HOXB1	1, 2
WBGene00000439	C13G5.1	ceh-16	HD - HOX	ENSP00000297375	EN2	1
WBGene00000442	F20D12.6	ceh-19	HD - HOX			2
WBGene00013583	Y80D3A.3	ceh-51	HD - HOX	ENSP00000344285		1, 2
WBGene00007417	C07E3.6	ceh-58	HD - HOX			1, 2
WBGene00011069	R06F6.6	ceh-62	HD - HOX			1
WBGene00044032	T21B4.17	ceh-99	HD - HOX
WBGene00001174	C08C3.1	egl-5	HD - HOX			1, 2
WBGene00003024	C07H6.7	lin-39	HD - HOX	ENSP00000239151	HOXB5	1, 2
WBGene00003102	C08C3.3	mab-5	HD - HOX	ENSP00000239165	HOXB7	1
WBGene00003779	Y75B8A.2	nob-1	HD - HOX	ENSP00000253572	CDX4	1, 2
WBGene00003912	C38D4.6	pal-1	HD - HOX	ENSP00000253572	CDX4	1
WBGene00004024	Y75B8A.1	php-3	HD - HOX	ENSP00000006015	HOXA11	1, 2
WBGene00006873	M142.4	vab-7	HD - HOX	ENSP00000312385	EVX2	1, 2
WBGene00022554	ZC204.2	duxl-1	HD - HOX - 2 domains	ENSP00000311467		1, 2
WBGene00000438	F46C8.5	ceh-14	HD - LIM	ENSP00000241587		1, 2
WBGene00002987	ZC64.4	lim-4	HD - LIM	ENSP00000271609	LHX9	1
WBGene00002988	K03E6.1	lim-6	HD - LIM	ENSP00000343711	LMX1B	1, 2
WBGene00002989	C04F1.3	lim-7	HD - LIM	ENSP00000290759	ISL2	1, 2
WBGene00003000	ZC247.3	lin-11	HD - LIM	ENSP00000254457	LHX1	1
WBGene00003167	F01D4.6	mec-3	HD - LIM			1
WBGene00006654	C40H5.5	ttx-3	HD - LIM	ENSP00000223522	LHX2	1
WBGene00000428	F16H11.4	ceh-1	HD - NK	ENSP00000332299
WBGene00000429	C27A12.5	ceh-2	HD - NK	ENSP00000258106	EMX1	1, 2
WBGene00000445	F29F11.5	ceh-22	HD - NK	ENSP00000246017	NKX2-2	1, 2
WBGene00000446	ZK652.5	ceh-23	HD - NK	ENSP00000302942	EMX2	1, 2
WBGene00000447	F55B12.1	ceh-24	HD - NK	ENSP00000346879	TITF1	1, 2
WBGene00000449	F46F3.1	ceh-27	HD - NK	ENSP00000238974	NKX2-3	2
WBGene00000450	K03A11.3	ceh-28	HD - NK	ENSP00000327758	NKX2-5	1
WBGene00000451	C33D12.7	ceh-30	HD - NK	ENSP00000263610	BARHL1
WBGene00000452	C33D12.1	ceh-31	HD - NK	ENSP00000263610	BARHL1	1
WBGene00000463	C28A5.4	ceh-43	HD - NK	ENSP00000222598	DLX5	1, 2
WBGene00000430	C16C2.1	ceh-5	HD - NK	ENSP00000234392	VAX2	1
WBGene00008242	C50H2.6	ceh-75	HD - NK
WBGene00000434	Y65B4BR.9	ceh-9	HD - NK
WBGene00000584	R03C1.3	cog-1	HD - NK	ENSP00000295886	NKX6-1	2
WBGene00003377	C39E6.4	mls-2	HD - NK	ENSP00000342854		1, 2
WBGene00004011	M6.3	pha-2	HD - NK	ENSP00000282728	HHEX
WBGene00006380	F31E8.3	tab-1	HD - NK	ENSP00000344285	1, 2
WBGene00006881	R07B1.1	vab-15	HD - NK	ENSP00000295284	MSX1	1, 2
WBGene00000441	ZC64.3	ceh-18	HD - POU	ENSP00000260264	POU2F3	1, 2
WBGene00000431	K02B12.1	ceh-6	HD - POU	ENSP00000355001	POU3F3	1
WBGene00009231	F28H6.2	ceh-89	HD - POU			1
WBGene00006818	C30A5.7	unc-86	HD - POU	ENSP00000230732	POU4F3	1
WBGene00012584	Y38E10A.6	ceh-100	HD - POU - 10 domains			1, 2
WBGene00018446	F45C12.15	ceh-83	HD - POU - 2 domains			1
WBGene00044330	R08B4.2	alr-1	HD - PRD	ENSP00000005545	ARX	2
WBGene00000435	W03A3.1	ceh-10	HD - PRD	ENSP00000261980	CHX10	1, 2
WBGene00000440	D1007.1	ceh-17	HD - PRD	ENSP00000298231	PHOX2A	1, 2
WBGene00000457	C37E2.4	ceh-36	HD - PRD	ENSP00000221996	CRX	1, 2
WBGene00000458	C37E2.5	ceh-37	HD - PRD	ENSP00000343819	OTX2	1, 2
WBGene00022837	ZK993.1	ceh-45	HD - PRD	ENSP00000238558	GSC	1
WBGene00015651	C09G12.1	ceh-53	HD - PRD	ENSP00000311290	PROP1	1
WBGene00016557	C40D2.4	ceh-84	HD - PRD
WBGene00001096	C18B12.3	dsc-1	HD - PRD	ENSP00000286667	ALX3	1, 2
WBGene00006652	Y113G7A.6	ttx-1	HD - PRD	ENSP00000282549	OTX1
WBGene00006766	B0564.10	unc-30	HD - PRD	ENSP00000323303	PITX1	1, 2
WBGene00006744	F26C11.2	unc-4	HD - PRD	ENSP00000005545	ARX	1, 2
WBGene00006778	F58E6.10	unc-42	HD - PRD	ENSP00000234492	PAX7	1, 2
WBGene00000433	ZK265.4	ceh-8	HD - PRD - 2 domains	ENSP00000334813	RAX	1, 2
WBGene00013147	Y53C12C.1	eyg-1	HD - PRD, Paired Domian - CPAX	ENSP00000337430	PAX6	1, 2
WBGene00003939	F27E5.2	pax-3	HD - PRD, Paired Domian - FULL	ENSP00000342092	PAX3	1, 2
WBGene00006870	F14F3.1	vab-3	HD - PRD, Paired Domian - FULL	ENSP00000337430	PAX6	1, 2
WBGene00000448	K12H4.1	ceh-26	HD - PROX	ENSP00000261454	PROX1	1
WBGene00000453	W05E10.3	ceh-32	HD - SIX	ENSP00000260653	SIX3	1, 2
WBGene00000454	C10G8.7	ceh-33	HD - SIX	ENSP00000247182	SIX1	1, 2
WBGene00000455	C10G8.6	ceh-34	HD - SIX			1, 2
WBGene00006775	F56A12.1	unc-39	HD - SIX			1, 2
WBGene00000443	F31E3.1	ceh-20	HD - TALE	ENSP00000275123	PBX2	1
WBGene00000461	F17A2.5	ceh-40	HD - TALE	ENSP00000275123	PBX2	1, 2
WBGene00008195	C49C3.5	ceh-88	HD - TALE			1, 2
WBGene00007984	C36F7.1	irx-1	HD - TALE	ENSP00000331608	IRX3	1, 2
WBGene00006796	T28F12.2	unc-62	HD - TALE	ENSP00000326296	MEIS2	1, 2
WBGene00017690	F22A3.5	ceh-60	HD -TALE	ENSP00000327400	PBX1	1
WBGene00001182	T22B7.1	egl-13	HMG box	ENSP00000344078		1, 2
WBGene00001560	T22H6.6	gei-3	HMG box	ENSP00000160740	CIC	1
WBGene00001971	Y48B6A.14	hmg-1.1	HMG box	ENSP00000296503	HMGB2	1, 2
WBGene00012209	W02D9.3	hmg-20	HMG box	ENSP00000336856	HMG20A	1, 2
WBGene00001973	C32F10.5	hmg-3	HMG box	ENSP00000278412	SSRP1	1, 2
WBGene00001974	T20B12.8	hmg-4	HMG box	ENSP00000278412	SSRP1	1, 2
WBGene00009827	F47G4.6	hmg-6	HMG box			1, 2
WBGene00004077	W10C8.2	pop-1	HMG box	ENSP00000344823		1, 2
WBGene00004771	C32E12.5	sem-2	HMG box	ENSP00000322568	SOX11
WBGene00004949	K08A8.2	sox-2	HMG box	ENSP00000323588	SOX2	1, 2
WBGene00004950	F40E10.2	sox-3	HMG box	ENSP00000245342	SOX21	1, 2
WBGene00015716	C12D12.5	sox-4	HMG box	ENSP00000293894	SOX8	1
WBGene00022182	Y71H2AM.17	swsn-3	HMG box	ENSP00000323967	SMARCE1	1
WBGene00001972	F47D12.4	hmg-1.2	HMG box - 2 domains	ENSP00000296503	HMGB2	1, 2
WBGene00001975	F45E4.9	hmg-5	HMG box - 2 domains	ENSP00000320311	TFAM	1, 2
WBGene00010566	K04G2.7	K04G2.7	HTH
WBGene00003148	H21P03.1	mbf-1	HTH	ENSP00000224073	EDF1	1, 2
WBGene00011315	T01C1.2	mbr-1	HTH	ENSP00000352150		1
WBGene00021679	Y48G1C.6	Y48G1C.6	HTH
WBGene00021808	Y53G8AM.8	Y53G8AM.8	HTH
WBGene00009009	F21D5.4	F21D5.4	HTH, Brinker
WBGene00020959	W02H5.4	W02H5.4	HTH, Brinker
WBGene00020251	T05C1.4	camt-1	IPT/TIG	ENSP00000306522	CAMTA1	1, 2
WBGene00002245	K08B4.1	lag-1	IPT/TIG	ENSP00000354528	RBPSUH	1, 2
WBGene00006743	Y16B4A.1	unc-3	IPT/TIG	ENSP00000322898	EBF	1, 2
WBGene00021942	Y55F3BR.5	madf-1	MADF			1, 2
WBGene00013717	Y106G6H.4	madf-10	MADF			1, 2
WBGene00015468	C05D2.6	madf-11	MADF
WBGene00009461	F36D1.1	madf-2	MADF			1, 2
WBGene00011575	T07C12.11	madf-4	MADF			1
WBGene00007242	C01G12.1	madf-5	MADF			1
WBGene00016930	C54G6.1	madf-6	MADF
WBGene00015502	C06A5.4	madf-7	MADF			2
WBGene00008118	C46F11.3	madf-8	MADF			1, 2
WBGene00022608	ZC416.1	madf-9	MADF			1, 2
WBGene00019218	H20J04.3	madf-3	MADF - 2 domains			2
WBGene00003182	W10D5.1	mef-2	MADS box	ENSP00000346389	MEF2A	1, 2
WBGene00006844	D1081.2	unc-120	MADS box	ENSP00000265354	SRF	1, 2
WBGene00000899	F25E2.5	daf-3	MH1	ENSP00000341551	SMAD4	1
WBGene00000904	R05D11.1	daf-8	MH1	ENSP00000239886	SMAD9	1, 2
WBGene00003592	ZK1290.4	nfi-1	MH1	ENSP00000342859	NFIC	1
WBGene00004856	ZK370.2	sma-2	MH1	ENSP00000305769	SMAD1	1, 2
WBGene00004857	R13F6.9	sma-3	MH1	ENSP00000231589	SMAD5	1, 2
WBGene00004858	R12B2.1	sma-4	MH1	ENSP00000341551	SMAD4	1, 2
WBGene00006445	F37D6.6	tag-68	MH1			1, 2
WBGene00015091	B0261.1	B0261.1	MYB	ENSP00000351575	BDP1	1, 2
WBGene00007053	T04D1.4	chd-7	MYB	ENSP00000307304	CHD7
WBGene00013676	Y105E8A.17	ekl-4	MYB	ENSP00000354697	DMAP1	1, 2
WBGene00017352	F10E7.11	F10E7.11	MYB	ENSP00000346400		1
WBGene00004203	Y113G7B.23	psa-1	MYB	ENSP00000346311	SMARCC1	2
WBGene00020111	R151.8	R151.8	MYB	ENSP00000348903		1
WBGene00020320	T07F8.4	T07F8.4	MYB	ENSP00000346400		1, 2
WBGene00008386	D1081.8	D1081.8	MYB - 2 domains	ENSP00000265414	CDC5L	1, 2
WBGene00001029	F38A5.13	dnj-11	MYB - 2 domains	ENSP00000249270	ZRF1	1, 2
WBGene00018836	F54F2.9	F54F2.9	MYB - 2 domains	ENSP00000259293	DNAJC1	1, 2
WBGene00001565	C14B9.6	gei-8	MYB - 2 domains	ENSP00000268712	NCOR1	1, 2
WBGene00005006	D1014.8	spr-1	MYB - 2 domains	ENSP00000262241	RCOR1	1, 2
WBGene00001568	F32H2.1	gei-11	MYB - 5 domains	ENSP00000298532	SNAPC4	1, 2
WBGene00015075	B0238.11	B0238.11	novel			1, 2
WBGene00016310	C32D5.1	C32D5.1	novel			1, 2
WBGene00016725	C46H3.2	C46H3.2	novel			1, 2
WBGene00001155	T05G5.6	ech-6	novel			1, 2
WBGene00001377	C49A1.4	eya-1	novel			2
WBGene00008587	F08G12.3	F08G12.3	novel			1, 2
WBGene00010353	H02I12.5	H02I12.5	novel			1, 2
WBGene00003003	T25C12.1	lin-14	novel			1, 2
WBGene00003037	JC8.6	lin-54	novel			1, 2
WBGene00004194	C34C6.6	prx-5	novel			1, 2
WBGene00011060	R06C1.6	R06C1.6	novel			1
WBGene00004764	K04G11.2	sel-7	novel			1, 2
WBGene00011864	T20F10.2	T20F10.2	novel			1, 2
WBGene00020758	T24C4.2	T24C4.2	novel			2
WBGene00014232	ZK1128.6	ttll-4	novel			1
WBGene00012471	Y17G7B.20	Y17G7B.20	novel
WBGene00012551	Y37D8A.11	Y37D8A.11	novel			1, 2
WBGene00021411	Y38C9A.1	Y38C9A.1	novel			1, 2
WBGene00013380	Y62E10A.14	Y62E10A.14	novel			2
WBGene00022042	Y65B4BR.5	Y65B4BR.5	novel	ENSP00000349212	NACA	1, 2
WBGene00022562	ZC204.12	ZC204.12	novel			1, 2
WBGene00014253	ZK1320.3	ZK1320.3	novel			1, 2
WBGene00006999	F42G4.3	zyx-1	novel			1, 2
WBGene00000467	F52B5.5	cep-1	p53			1, 2
WBGene00008999	F21A10.2	F21A10.2	p53	ENSP00000265460		1, 2
WBGene00004134	F59B10.1	pqn-47	p53	ENSP00000265460		1
WBGene00000938	C26C6.5	dcp-66	p66 family			1, 2
WBGene00001204	C04G2.7	egl-38	Paired Domain - FULL	ENSP00000346455	PAX5	1, 2
WBGene00003937	K07C11.1	pax-1	Paired Domain - FULL	ENSP00000246010	PAX1	1, 2
WBGene00003938	K06B9.5	pax-2	Paired Domain - FULL	ENSP00000347385	PAX2	1
WBGene00017664	F21D12.5	npax-1	Paired Domain - NPAX			1, 2
WBGene00018591	F48B9.5	npax-2	Paired Domain - NPAX			1, 2
WBGene00011257	R13.2	npax-3	Paired Domain - NPAX			1, 2
WBGene00007496	C09G9.7	npax-4	Paired Domain - NPAX			1, 2
WBGene00008976	F20D1.4	F20D1.4	PUR			1, 2
WBGene00004046	F45E4.2	plp-1	PUR			2
WBGene00004393	B0414.2	rnt-1	RNT	ENSP00000319087		1, 2
WBGene00009174	F26H9.2	F26H9.2	RPEL - 2 domains	ENSP00000305530	PHACTR2
WBGene00015285	C01B12.2	gmeb-1	SAND	ENSP00000266068	GMEB2	1
WBGene00010010	F53H4.5	gmeb-2	SAND	ENSP00000266068	GMEB2	1, 2
WBGene00013111	Y51H4A.17	sta-1	STAT	ENSP00000300134	STAT6	1, 2
WBGene00003106	T27A1.6	mab-9	T-box	ENSP00000297053	TBX20	1, 2
WBGene00003376	H14A12.4	mls-1	T-box	ENSP00000331791		1, 2
WBGene00004750	F19B10.9	sea-1	T-box			1, 2
WBGene00006547	F40H6.4	tbx-11	T-box			1, 2
WBGene00006543	F21H11.3	tbx-2	T-box	ENSP00000257567		1, 2
WBGene00006549	Y59E9AR.3	tbx-30	T-box			1
WBGene00006550	C36C9.2	tbx-31	T-box			1
WBGene00006551	ZK380.1	tbx-32	T-box			1
WBGene00006552	Y66A7A.8	tbx-33	T-box			1
WBGene00006553	Y47D3A.10	tbx-34	T-box			2
WBGene00006554	ZK177.10	tbx-35	T-box			1
WBGene00006555	ZK829.5	tbx-36	T-box			1, 2
WBGene00006556	Y47D3A.12	tbx-37	T-box	ENSP00000177694	TBX21
WBGene00006557	C24H11.3	tbx-38	T-box	ENSP00000279386	TBX6	1, 2
WBGene00006558	Y73F8A.16	tbx-39	T-box			2
WBGene00006559	Y73F8A.17	tbx-40	T-box			2
WBGene00006560	T26C11.1	tbx-41	T-box			1
WBGene00022000	Y59E9AR.5	tbx-42	T-box
WBGene00044798	Y46E12A.4	tbx-43	T-box
WBGene00006544	ZK328.8	tbx-7	T-box	ENSP00000240328	TBX2
WBGene00006545	T07C4.2	tbx-8	T-box			1
WBGene00006546	T07C4.6	tbx-9	T-box			1
WBGene00001208	F28B12.2	egl-44	TEA/ATTS	ENSP00000351184	TEAD4	1
WBGene00001081	F47A4.2	dpy-22	TRAP230 family			1
WBGene00016272	C30G4.7	C30G4.7	TSC-22/dip/bun	ENSP00000261489
WBGene00011824	T18D3.7	T18D3.7	TSC-22/dip/bun	ENSP00000261489		1, 2
WBGene00012994	Y48C3A.12	Y48C3A.12	TSC-22/dip/bun	ENSP00000354885		2
WBGene00001820	F53B2.6	ham-1	WH			1, 2
WBGene00003241	T05C12.6	mig-5	WH			1, 2
WBGene00000895	B0412.1	dac-1	WH - DAC	ENSP00000346604		1, 2
WBGene00020368	T08H4.3	ast-1	WH - ETS	ENSP00000339627	FLI1	2
WBGene00016029	C24A1.2	elf-1	WH - ETS	ENSP00000239882	ELF1	2
WBGene00006462	C33A11.4	ets-3	WH - ETS	ENSP00000257831	EHF	1, 2
WBGene00017687	F22A3.1	ets-4	WH - ETS	ENSP00000315408	SPDEF	1
WBGene00016600	C42D8.4	ets-5	WH - ETS	ENSP00000295727	FEV	1, 2
WBGene00017598	F19F10.1	ets-6	WH - ETS	ENSP00000349966	ERG	1, 2
WBGene00017601	F19F10.5	ets-7	WH - ETS	ENSP00000281428		1
WBGene00016798	C50A2.4	ets-8	WH - ETS	ENSP00000345585
WBGene00016865	C52B9.2	ets-9	WH - ETS	ENSP00000222279	ETV2	1, 2
WBGene00002990	C37F5.1	lin-1	WH - ETS	ENSP00000228741	ELK3	1
WBGene00007907	C34B4.2	C34B4.2	WH - Fork Head
WBGene00001442	C25A1.2	fkh-10	WH - Fork Head			1
WBGene00001434	T14G12.4	fkh-2	WH - Fork Head	ENSP00000339004	FOXG1C	1, 2
WBGene00001435	C29F7.4	fkh-3	WH - Fork Head			2
WBGene00001436	C29F7.5	fkh-4	WH - Fork Head			1
WBGene00001437	F26A1.2	fkh-5	WH - Fork Head			1, 2
WBGene00001438	B0286.5	fkh-6	WH - Fork Head	ENSP00000064324	FOXC1	1, 2
WBGene00001440	F40H3.4	fkh-8	WH - Fork Head	ENSP00000354449		1, 2
WBGene00001441	K03C7.2	fkh-9	WH - Fork Head
WBGene00010553	K04C1.3	K04C1.3	WH - Fork Head			1
WBGene00002601	F26B1.7	let-381	WH - Fork Head	ENSP00000259806	FOXF2	1
WBGene00003017	K10G6.1	lin-31	WH - Fork Head	ENSP00000306807	FOXB1	1, 2
WBGene00003976	T28H11.4	pes-1	WH - Fork Head	ENSP00000306807	FOXB1	1, 2
WBGene00004013	F38A6.1	pha-4	WH - Fork Head	ENSP00000250448	FOXA1	1, 2
WBGene00012074	T27A8.2	T27A8.2	WH - Fork Head			1, 2
WBGene00006853	C47G2.2	unc-130	WH - Fork Head	ENSP00000334691	FOXD3	1, 2
WBGene00000912	R13H8.1	daf-16	WH - Fork Head, AT Hook	ENSP00000339527	FOXO3A	1, 2
WBGene00002004	Y53C10A.12	hsf-1	WH - HSF	ENSP00000332698	HSF1	1
WBGene00013134	Y53C10A.3	hsf-2	WH - HSF			1
WBGene00044805	Y53C10A.15	Y53C10A.15	WH - HSF
WBGene00000914	F33H1.1	daf-19	WH - RFX	ENSP00000352076		1
WBGene00001061	T23G7.1	dpl-1	WH - TDP	ENSP00000352355	TFDP1	1, 2
WBGene00001161	Y102A5C.18	efl-1	WH - TDP	ENSP00000256117	E2F5	1
WBGene00001162	Y48C3A.17	efl-2	WH - TDP	ENSP00000262904	E2F3	2
WBGene00009899	F49E12.6	efl-3	WH - TDP - 2 domains	ENSP00000250024		1, 2
WBGene00007645	C17E4.6	C17E4.6	YL1 TF	ENSP00000295315	TCFL1	1, 2
WBGene00012674	Y39B6A.12	bed-1	ZF - BED			1, 2
WBGene00012943	Y47D3B.9	bed-2	ZF - BED			1, 2
WBGene00009133	F25H8.6	bed-3	ZF - BED			2
WBGene00001570	F58A4.11	gei-13	ZF - BED			1
WBGene00010704	K09A11.1	K09A11.1	ZF - BED	ENSP00000216268	ZBED4	1, 2
WBGene00020396	T10B5.10	T10B5.10	ZF - BED
WBGene00013639	Y105C5A.15	Y105C5A.15	ZF - BED			1, 2
WBGene00014060	ZK673.4	ZK673.4	ZF - BED
WBGene00001079	T22B3.1	dpy-20	ZF - BED x2			1
WBGene00003021	F44B9.6	lin-36	ZF - C2CH - 1 finger, ZF - THAP			1, 2
WBGene00044386	C27A2.7	C27A2.7	ZF - C2H2
WBGene00044791	F55C5.11	F55C5.11	ZF - C2H2
WBGene00004747	C25D7.3	sdc-3	ZF - C2H2			1, 2
WBGene00007063	2L52.1	2L52.1	ZF - C2H2 - 1 finger			1
WBGene00013595	Y87G2A.3	atg-4.1	ZF - C2H2 - 1 finger	ENSP00000355256	APG4A	2
WBGene00007223	C01F6.9	C01F6.9	ZF - C2H2 - 1 finger	ENSP00000311768		1, 2
WBGene00015352	C02F5.12	C02F5.12	ZF - C2H2 - 1 finger
WBGene00015527	C06E2.1	C06E2.1	ZF - C2H2 - 1 finger			1, 2
WBGene00016427	C34H4.5	C34H4.5	ZF - C2H2 - 1 finger
WBGene00008007	C38D4.7	C38D4.7	ZF - C2H2 - 1 finger			1, 2
WBGene00016712	C46E10.8	C46E10.8	ZF - C2H2 - 1 finger			1, 2
WBGene00016888	C52E12.1	C52E12.1	ZF - C2H2 - 1 finger	ENSP00000248125	ZNF598
WBGene00019629	K10D2.3	cid-1	ZF - C2H2 - 1 finger	ENSP00000311339	ZCCHC6	1, 2
WBGene00008363	D1046.2	D1046.2	ZF - C2H2 - 1 finger			1, 2
WBGene00008417	D2030.7	D2030.7	ZF - C2H2 - 1 finger			1, 2
WBGene00016200	C28H8.9	dpff-1	ZF - C2H2 - 1 finger	ENSP00000252268	DPF2	1, 2
WBGene00011696	T10G3.5	eea-1	ZF - C2H2 - 1 finger	ENSP00000317955	EEA1	1
WBGene00001210	K11G9.4	egl-46	ZF - C2H2 - 1 finger	ENSP00000306523	INSM2	1
WBGene00043705	Y55F3AM.7	egrh-2	ZF - C2H2 - 1 finger
WBGene00009014	F21D5.9	F21D5.9	ZF - C2H2 - 1 finger			1
WBGene00009026	F21G4.5	F21G4.5	ZF - C2H2 - 1 finger			1, 2
WBGene00009190	F27D4.6	F27D4.6	ZF - C2H2 - 1 finger			1, 2
WBGene00018140	F37B4.10	F37B4.10	ZF - C2H2 - 1 finger			1
WBGene00018248	F40G9.14	F40G9.14	ZF - C2H2 - 1 finger			1
WBGene00009687	F44D12.10	F44D12.10	ZF - C2H2 - 1 finger			1
WBGene00018432	F45C12.1	F45C12.1	ZF - C2H2 - 1 finger			1
WBGene00018636	F49E8.2	F49E8.2	ZF - C2H2 - 1 finger			1
WBGene00009923	F52B5.7	F52B5.7	ZF - C2H2 - 1 finger
WBGene00009965	F53B7.2	F53B7.2	ZF - C2H2 - 1 finger
WBGene00010086	F55B11.4	F55B11.4	ZF - C2H2 - 1 finger			1, 2
WBGene00050929	F58D12.5	F58D12.5	ZF - C2H2 - 1 finger
WBGene00010453	K01B6.1	fozi-1	ZF - C2H2 - 1 finger			1, 2
WBGene00001867	T07G12.12	him-8	ZF - C2H2 - 1 finger			1
WBGene00019407	K05F1.5	K05F1.5	ZF - C2H2 - 1 finger	ENSP00000274507	LECT2	1
WBGene00019651	K11D12.12	K11D12.12	ZF - C2H2 - 1 finger
WBGene00010781	K11H3.4	K11H3.4	ZF - C2H2 - 1 finger
WBGene00019691	K12H6.12	K12H6.12	ZF - C2H2 - 1 finger			1, 2
WBGene00003012	F18A1.2	lin-26	ZF - C2H2 - 1 finger			1, 2
WBGene00003044	F18A1.3	lir-1	ZF - C2H2 - 1 finger			1, 2
WBGene00003045	F18A1.4	lir-2	ZF - C2H2 - 1 finger			1, 2
WBGene00003046	F37H8.1	lir-3	ZF - C2H2 - 1 finger			1, 2
WBGene00013096	Y51H1A.6	mcd-1	ZF - C2H2 - 1 finger			1, 2
WBGene00004111	C37A2.5	pqn-21	ZF - C2H2 - 1 finger			1, 2
WBGene00019824	R02D3.7	R02D3.7	ZF - C2H2 - 1 finger			1, 2
WBGene00019878	R05D3.3	R05D3.3	ZF - C2H2 - 1 finger			1, 2
WBGene00011113	R07E5.5	R07E5.5	ZF - C2H2 - 1 finger			1
WBGene00021538	Y42H9AR.3	rabs-5	ZF - C2H2 - 1 finger	ENSP00000253699	ZFYVE20	2
WBGene00008683	F11A10.2	repo-1	ZF - C2H2 - 1 finger	ENSP00000221494	SF3A2	1
WBGene00004751	K10G6.3	sea-2	ZF - C2H2 - 1 finger			1
WBGene00010868	M04G12.4	somi-1	ZF - C2H2 - 1 finger			1
WBGene00009743	F45H11.1	sptf-1	ZF - C2H2 - 1 finger	ENSP00000297210		1, 2
WBGene00015447	C04F5.5	srab-2	ZF - C2H2 - 1 finger			1
WBGene00012976	Y48A6C.3	sup-35	ZF - C2H2 - 1 finger			1, 2
WBGene00011547	T06G6.5	T06G6.5	ZF - C2H2 - 1 finger			1
WBGene00011626	T08G5.7	T08G5.7	ZF - C2H2 - 1 finger
WBGene00011924	T22C8.3	T22C8.3	ZF - C2H2 - 1 finger			1, 2
WBGene00011925	T22C8.4	T22C8.4	ZF - C2H2 - 1 finger			1
WBGene00011956	T23F11.4	T23F11.4	ZF - C2H2 - 1 finger			1, 2
WBGene00006580	T23G4.1	tlp-1	ZF - C2H2 - 1 finger	ENSP00000312257	ZNF503	1, 2
WBGene00017733	F23C8.4	ubxn-1	ZF - C2H2 - 1 finger	ENSP00000294119		1, 2
WBGene00021019	W04B5.2	W04B5.2	ZF - C2H2 - 1 finger			1
WBGene00012243	W04D2.4	W04D2.4	ZF - C2H2 - 1 finger			1
WBGene00021387	Y37F4.6	Y37F4.6	ZF - C2H2 - 1 finger
WBGene00021637	Y47G6A.7	Y47G6A.7	ZF - C2H2 - 1 finger	ENSP00000243896	SLC35C2
WBGene00012974	Y48A6C.1	Y48A6C.1	ZF - C2H2 - 1 finger	ENSP00000318024		1
WBGene00013006	Y48E1B.7	Y48E1B.7	ZF - C2H2 - 1 finger			1
WBGene00013128	Y52B11A.9	Y52B11A.9	ZF - C2H2 - 1 finger	ENSP00000281372	KIN	1, 2
WBGene00013152	Y53F4B.5	Y53F4B.5	ZF - C2H2 - 1 finger			1
WBGene00013178	Y53H1A.2	Y53H1A.2	ZF - C2H2 - 1 finger			1
WBGene00021885	Y54G2A.20	Y54G2A.20	ZF - C2H2 - 1 finger
WBGene00013236	Y56A3A.18	Y56A3A.18	ZF - C2H2 - 1 finger	ENSP00000270812	ZNF593	1, 2
WBGene00013270	Y57A10A.31	Y57A10A.31	ZF - C2H2 - 1 finger	ENSP00000299305	ARIH1	1, 2
WBGene00022349	Y82E9BR.17	Y82E9BR.17	ZF - C2H2 - 1 finger			1
WBGene00011597	T07G12.6	zim-1	ZF - C2H2 - 1 finger			1, 2
WBGene00011600	T07G12.10	zim-2	ZF - C2H2 - 1 finger			1
WBGene00011601	T07G12.11	zim-3	ZF - C2H2 - 1 finger			1, 2
WBGene00022671	ZK177.3	ZK177.3	ZF - C2H2 - 1 finger			1, 2
WBGene00022681	ZK185.1	ZK185.1	ZF - C2H2 - 1 finger			1, 2
WBGene00022785	ZK652.6	ZK652.6	ZF - C2H2 - 1 finger	ENSP00000319986	KCMF1	1, 2
WBGene00022794	ZK686.4	ZK686.4	ZF - C2H2 - 1 finger	ENSP00000274712	ZMAT2	1
WBGene00010936	M163.2	ztf-14	ZF - C2H2 - 1 finger	ENSP00000265526	GLI3
WBGene00020763	T24C4.7	ztf-18	ZF - C2H2 - 1 finger			1, 2
WBGene00012988	Y48C3A.4	ztf-22	ZF - C2H2 - 1 finger			2
WBGene00011661	T09F3.1	ztf-27	ZF - C2H2 - 1 finger			1, 2
WBGene00016905	C53D5.4	ztf-3	ZF - C2H2 - 1 finger			1, 2
WBGene00020399	T10B11.3	ztf-4	ZF - C2H2 - 1 finger			1, 2
WBGene00009365	F33H1.4	F33H1.4	ZF - C2H2 - 1 finger, AT Hook x3			1
WBGene00007042	C26C6.1	pbrm-1	ZF - C2H2 - 1 finger, HMG box	ENSP00000349213		1
WBGene00017967	F32A5.1	ada-2	ZF - C2H2 - 1 finger, MYB	ENSP00000308022		1
WBGene00010012	F53H10.2	saeg-1	ZF - C2H2 - 1 finger, MYB	ENSP00000346285
WBGene00001439	F26D12.1	fkh-7	ZF - C2H2 - 1 finger, WH - Fork Head	ENSP00000353689	FOXP4	1
WBGene00021689	Y48G8AL.10	Y48G8AL.10	ZF - C2H2 - 12 fingers	ENSP00000306351
WBGene00005009	C09H6.1	spr-4	ZF - C2H2 - 14 fingers	ENSP00000337455	ZNF142	1, 2
WBGene00003002	C03B8.4	lin-13	ZF - C2H2 - 15 fingers	ENSP00000284020
WBGene00007105	B0035.1	B0035.1	ZF - C2H2 - 2 fingers	ENSP00000340029	ZNF207	1, 2
WBGene00015138	B0310.2	B0310.2	ZF - C2H2 - 2 fingers			1
WBGene00015620	C08G9.2	C08G9.2	ZF - C2H2 - 2 fingers			1, 2
WBGene00001035	T03F6.2	dnj-17	ZF - C2H2 - 2 fingers	ENSP00000343728		1
WBGene00017651	F21A9.2	F21A9.2	ZF - C2H2 - 2 fingers			2
WBGene00018420	F44E2.7	F44E2.7	ZF - C2H2 - 2 fingers			1, 2
WBGene00001821	C07A12.1	ham-2	ZF - C2H2 - 2 fingers			1, 2
WBGene00019598	K09H9.7	K09H9.7	ZF - C2H2 - 2 fingers			1
WBGene00019611	K10B3.5	K10B3.5	ZF - C2H2 - 2 fingers			1, 2
WBGene00009834	F47H4.1	lsy-27	ZF - C2H2 - 2 fingers			1, 2
WBGene00011206	R10E4.11	R10E4.11	ZF - C2H2 - 2 fingers			1
WBGene00020093	R144.3	R144.3	ZF - C2H2 - 2 fingers			1
WBGene00016948	C55C2.1	scrt-1	ZF - C2H2 - 2 fingers
WBGene00004745	F52E10.1	sdc-1	ZF - C2H2 - 2 fingers			1
WBGene00014131	ZK892.7	sdz-38	ZF - C2H2 - 2 fingers			1, 2
WBGene00020630	T20F7.1	T20F7.1	ZF - C2H2 - 2 fingers			1, 2
WBGene00020635	T20H4.2	T20H4.2	ZF - C2H2 - 2 fingers			1, 2
WBGene00021000	W03F9.2	W03F9.2	ZF - C2H2 - 2 fingers			1, 2
WBGene00012473	Y17G7B.22	Y17G7B.22	ZF - C2H2 - 2 fingers
WBGene00021254	Y22D7AL.16	Y22D7AL.16	ZF - C2H2 - 2 fingers			1
WBGene00021688	Y48G8AL.9	Y48G8AL.9	ZF - C2H2 - 2 fingers
WBGene00021704	Y48G9A.11	Y48G9A.11	ZF - C2H2 - 2 fingers			1
WBGene00013240	Y56A3A.28	Y56A3A.28	ZF - C2H2 - 2 fingers	ENSP00000323945		1
WBGene00013505	Y71A12B.8	Y71A12B.8	ZF - C2H2 - 2 fingers
WBGene00022334	Y82E9BR.1	Y82E9BR.1	ZF - C2H2 - 2 fingers			1
WBGene00022387	Y95B8A.7	Y95B8A.7	ZF - C2H2 - 2 fingers	ENSP00000265069		1
WBGene00018704	F52E4.8	ztf-13	ZF - C2H2 - 2 fingers			1
WBGene00011639	T09A5.12	ztf-17	ZF - C2H2 - 2 fingers			1, 2
WBGene00012405	Y6G8.3	ztf-25	ZF - C2H2 - 2 fingers			1, 2
WBGene00018099	F36F12.8	ztf-28	ZF - C2H2 - 2 fingers			1, 2
WBGene00013438	Y66D12A.12	ztf-29	ZF - C2H2 - 2 fingers
WBGene00015523	C06E1.8	ztf-30	ZF - C2H2 - 2 fingers			1
WBGene00012317	W06H12.1	ztf-6	ZF - C2H2 - 2 fingers	ENSP00000354487		1, 2
WBGene00007433	C08B11.3	C08B11.3	ZF - C2H2 - 2 fingers, ARID/BRIGHT	ENSP00000335044	ARID2	1
WBGene00015451	C04F5.9	C04F5.9	ZF - C2H2 - 3 fingers			1, 2
WBGene00015809	C16A3.4	C16A3.4	ZF - C2H2 - 3 fingers	ENSP00000310042	ZNF622	1, 2
WBGene00000995	C18D1.1	die-1	ZF - C2H2 - 3 fingers			1, 2
WBGene00007772	C27C12.2	egrh-1	ZF - C2H2 - 3 fingers	ENSP00000239938	EGR1	1, 2
WBGene00044651	Y94H6A.11	egrh-3	ZF - C2H2 - 3 fingers
WBGene00017430	F13H6.1	F13H6.1	ZF - C2H2 - 3 fingers	ENSP00000280435		1
WBGene00017814	F26A10.2	F26A10.2	ZF - C2H2 - 3 fingers	ENSP00000221355		1, 2
WBGene00018567	F47E1.3	F47E1.3	ZF - C2H2 - 3 fingers	ENSP00000276594	PRDM14	1
WBGene00019011	F57C9.4	F57C9.4	ZF - C2H2 - 3 fingers			1, 2
WBGene00010770	K11D2.4	K11D2.4	ZF - C2H2 - 3 fingers	ENSP00000309784	ZNF32	1
WBGene00018990	F56F11.3	klf-1	ZF - C2H2 - 3 fingers	ENSP00000259349	KLF4	1, 2
WBGene00009998	F53F8.1	klf-2	ZF - C2H2 - 3 fingers	ENSP00000261438	KLF3	1
WBGene00003480	F54H5.4	klf-3	ZF - C2H2 - 3 fingers	ENSP00000350807	KLF8	2
WBGene00003380	C10A4.8	mnm-2	ZF - C2H2 - 3 fingers			1, 2
WBGene00003845	B0280.4	odd-1	ZF - C2H2 - 3 fingers			1, 2
WBGene00003846	C34H3.2	odd-2	ZF - C2H2 - 3 fingers	ENSP00000297565	OSR2	1, 2
WBGene00004096	F40F8.7	pqm-1	ZF - C2H2 - 3 fingers			1, 2
WBGene00004335	C47C12.3	ref-2	ZF - C2H2 - 3 fingers	ENSP00000282928	ZIC1	1, 2
WBGene00013350	Y59A8B.13	slr-2	ZF - C2H2 - 3 fingers	ENSP00000349161
WBGene00011926	T22C8.5	sptf-2	ZF - C2H2 - 3 fingers	ENSP00000222584	SP4	1, 2
WBGene00012735	Y40B1A.4	sptf-3	ZF - C2H2 - 3 fingers	ENSP00000310301	SP3	1, 2
WBGene00006827	F08C6.7	unc-98	ZF - C2H2 - 3 fingers	ENSP00000271977		1, 2
WBGene00020942	W02D7.6	W02D7.6	ZF - C2H2 - 3 fingers			1, 2
WBGene00021374	Y37E11B.1	Y37E11B.1	ZF - C2H2 - 3 fingers			1, 2
WBGene00013465	Y67H2A.10	Y67H2A.10	ZF - C2H2 - 3 fingers
WBGene00013537	Y73F8A.33	Y73F8A.33	ZF - C2H2 - 3 fingers
WBGene00013580	Y79H2A.3	Y79H2A.3	ZF - C2H2 - 3 fingers			1
WBGene00022592	ZC328.2	ZC328.2	ZF - C2H2 - 3 fingers	ENSP00000331067	ZNF25	1
WBGene00022762	ZK546.5	ZK546.5	ZF - C2H2 - 3 fingers			1
WBGene00022795	ZK686.5	ZK686.5	ZF - C2H2 - 3 fingers
WBGene00020848	T27B1.2	ztf-19	ZF - C2H2 - 3 fingers			1
WBGene00008762	F13G3.1	ztf-2	ZF - C2H2 - 3 fingers	ENSP00000252713	ZNF655	1, 2
WBGene00012702	Y39B6A.46	ztf-20	ZF - C2H2 - 3 fingers			2
WBGene00010137	F55H12.6	ztf-26	ZF - C2H2 - 3 fingers
WBGene00022598	ZC395.8	ztf-8	ZF - C2H2 - 3 fingers			1, 2
WBGene00013966	ZK287.6	ztf-9	ZF - C2H2 - 3 fingers			1
WBGene00018794	F54C4.3	attf-3	ZF - C2H2 - 3 fingers, AT Hook			1
WBGene00003847	F25D7.3	blmp-1	ZF - C2H2 - 4 fingers	ENSP00000071246	PRDM1	1, 2
WBGene00016713	C46E10.9	C46E10.9	ZF - C2H2 - 4 fingers			1, 2
WBGene00016890	C52E12.6	C52E12.6	ZF - C2H2 - 4 fingers
WBGene00000468	F43G9.11	ces-1	ZF - C2H2 - 4 fingers	ENSP00000340112		1, 2
WBGene00000483	C55B7.12	che-1	ZF - C2H2 - 4 fingers	ENSP00000350492	ZNF79	1, 2
WBGene00001207	R53.3	egl-43	ZF - C2H2 - 4 fingers	ENSP00000270722	PRDM16	1, 2
WBGene00008640	F10B5.3	F10B5.3	ZF - C2H2 - 4 fingers			1, 2
WBGene00018959	F56D1.1	F56D1.1	ZF - C2H2 - 4 fingers			1, 2
WBGene00010401	H16D19.3	H16D19.3	ZF - C2H2 - 4 fingers			2
WBGene00019299	K02D7.2	K02D7.2	ZF - C2H2 - 4 fingers	ENSP00000020945	SNAI2
WBGene00003033	F34D10.5	lin-48	ZF - C2H2 - 4 fingers	ENSP00000246049		1, 2
WBGene00044068	ZK867.1	syd-9	ZF - C2H2 - 4 fingers	ENSP00000324605	ZNF660	2
WBGene00011583	T07D10.3	T07D10.3	ZF - C2H2 - 4 fingers			1, 2
WBGene00013970	ZK337.2	ZK337.2	ZF - C2H2 - 4 fingers	ENSP00000239938	EGR1	1, 2
WBGene00018833	F54F2.5	ztf-1	ZF - C2H2 - 4 fingers			1, 2
WBGene00009772	F46B6.7	ztf-7	ZF - C2H2 - 4 fingers	ENSP00000354501	ZNF277	2
WBGene00006970	F28F9.1	zag-1	ZF - C2H2 - 4 fingers, HD - ZFHD	ENSP00000353778		1, 2
WBGene00016189	C28G1.4	C28G1.4	ZF - C2H2 - 5 fingers			1, 2
WBGene00009508	F37D6.2	F37D6.2	ZF - C2H2 - 5 fingers	ENSP00000267807	SUHW4	2
WBGene00003015	W03C9.4	lin-29	ZF - C2H2 - 5 fingers	ENSP00000291413		1, 2
WBGene00009937	F52F12.4	lsl-1	ZF - C2H2 - 5 fingers	ENSP00000321049	ZNF227	1, 2
WBGene00003087	F49H12.1	lsy-2	ZF - C2H2 - 5 fingers	ENSP00000319479	ZNF404	1, 2
WBGene00003218	M04B2.1	mep-1	ZF - C2H2 - 5 fingers			1, 2
WBGene00003909	F45B8.4	pag-3	ZF - C2H2 - 5 fingers	ENSP00000294702	GFI1	2
WBGene00006604	Y47D3A.6	tra-1	ZF - C2H2 - 5 fingers	ENSP00000312694		1, 2
WBGene00012639	Y38H8A.5	Y38H8A.5	ZF - C2H2 - 5 fingers	ENSP00000283268	ZNF312	1
WBGene00012385	Y5F2A.4	Y5F2A.4	ZF - C2H2 - 5 fingers			1, 2
WBGene00011066	R06C7.9	ztf-15	ZF - C2H2 - 5 fingers			1
WBGene00007121	B0250.4	B0250.4	ZF - C2H2 - 6 fingers			1, 2
WBGene00015649	C09F5.3	C09F5.3	ZF - C2H2 - 6 fingers	ENSP00000262383	ZNF423	1
WBGene00016154	C27A12.2	C27A12.2	ZF - C2H2 - 6 fingers			1, 2
WBGene00001223	ZK616.10	ehn-3	ZF - C2H2 - 6 fingers	ENSP00000343443	ZNF588	2
WBGene00005011	F26F4.8	F26F4.8	ZF - C2H2 - 6 fingers			1
WBGene00010264	F58G1.2	F58G1.2	ZF - C2H2 - 6 fingers			2
WBGene00019751	M03D4.4	M03D4.4	ZF - C2H2 - 6 fingers	ENSP00000345514		1, 2
WBGene00011505	T05G11.1	pzf-1	ZF - C2H2 - 6 fingers			1, 2
WBGene00006492	C27A12.3	tag-146	ZF - C2H2 - 6 fingers			1
WBGene00018740	F53B3.1	tra-4	ZF - C2H2 - 6 fingers			1, 2
WBGene00013734	Y111B2A.10	Y111B2A.10	ZF - C2H2 - 6 fingers			1
WBGene00015274	C01B7.1	ztf-12	ZF - C2H2 - 6 fingers			1
WBGene00021846	Y54E10BR.8	ztf-23	ZF - C2H2 - 6 fingers	ENSP00000339314	ZNF70	1, 2
WBGene00017406	F12E12.5	sdz-12	ZF - C2H2 - 7 fingers			2
WBGene00004773	F15C11.1	sem-4	ZF - C2H2 - 7 fingers	ENSP00000340501		1, 2
WBGene00004862	T05A10.1	sma-9	ZF - C2H2 - 7 fingers			1
WBGene00005008	C07A12.5	spr-3	ZF - C2H2 - 7 fingers			1
WBGene00009448	F35H8.3	zfp-2	ZF - C2H2 - 7 fingers			1, 2
WBGene00019960	R08E3.4	ztf-16	ZF - C2H2 - 8 fingers
WBGene00001324	R11E3.6	eor-1	ZF - C2H2 - 9 fingers	ENSP00000340307	MYNN	2
WBGene00009553	F39B2.1	F39B2.1	ZF - C2H2 - 9 fingers	ENSP00000318085		1, 2
WBGene00001824	F13D11.2	hbl-1	ZF - C2H2 - 9 fingers	ENSP00000337455	ZNF142	1, 2
WBGene00021931	Y55F3AM.14	Y55F3AM.14	ZF - C2H2 - 9 fingers	ENSP00000346382		2
WBGene00022518	ZC123.3	ZC123.3	ZF - C2H2 - 9 fingers, HD - 3 domains	ENSP00000050961	ZFHX4	1
WBGene00009939	F52F12.6	ztf-11	ZF - C2HC - 2 fingers	ENSP00000353269		1
WBGene00007929	C34D1.1	dmd-10	ZF - DM			1
WBGene00007930	C34D1.2	dmd-11	ZF - DM			1, 2
WBGene00012832	Y43F8C.10	dmd-3	ZF - DM			1
WBGene00007776	C27C12.6	dmd-4	ZF - DM	ENSP00000190165	DMRT3	1, 2
WBGene00017326	F10C1.5	dmd-5	ZF - DM	ENSP00000319651	DMRTA1	1, 2
WBGene00007058	F13G11.1	dmd-6	ZF - DM			1, 2
WBGene00019521	K08B12.2	dmd-7	ZF - DM
WBGene00022060	Y67D8A.3	dmd-9	ZF - DM			1
WBGene00003114	C32C4.5	mab-23	ZF - DM
WBGene00020708	T22H9.4	dmd-8	ZF - DM - 2 domains
WBGene00003100	Y53C12B.5	mab-3	ZF - DM - 2 domains			1, 2
WBGene00012435	Y11D7A.12	flh-1	ZF - FLYWCH			1, 2
WBGene00016138	C26E6.2	flh-2	ZF - FLYWCH			1
WBGene00012436	Y11D7A.13	flh-3	ZF - FLYWCH			1, 2
WBGene00003968	T14F9.4	peb-1	ZF - FLYWCH			1
WBGene00001186	F55A8.1	egl-18	ZF - GATA	ENSP00000345681	GATA2	1, 2
WBGene00001250	C33D3.1	elt-2	ZF - GATA			1, 2
WBGene00001251	K02B9.4	elt-3	ZF - GATA			1, 2
WBGene00001252	C39B10.6	elt-4	ZF - GATA
WBGene00001253	F52C12.5	elt-6	ZF - GATA	ENSP00000218266	GATA1	1, 2
WBGene00015981	C18G1.2	elt-7	ZF - GATA			2
WBGene00001310	F58E10.2	end-1	ZF - GATA			1, 2
WBGene00001311	F58E10.5	end-3	ZF - GATA			1, 2
WBGene00003180	T24D3.1	med-1	ZF - GATA			1
WBGene00003181	K04C2.6	med-2	ZF - GATA
WBGene00001249	W09C2.1	elt-1	ZF - GATA - 2 domains	ENSP00000218266	GATA1	1, 2
WBGene00001194	C04A2.3	egl-27	ZF - GATA, MYB	ENSP00000338629	RERE	1
WBGene00003025	T27C4.4	lin-40	ZF - GATA, MYB	ENSP00000282366	MTA3	1, 2
WBGene00022278	Y74C9A.4	Y74C9A.4	ZF - GATA, MYB (2x)	ENSP00000326840	RCOR3	2
WBGene00007048	C16A3.7	nfx-1	ZF - NF-X1 - 10 domains	ENSP00000353576		1
WBGene00014208	ZK1067.2	ZK1067.2	ZF - NF-X1 - 2 domains	ENSP00000244030
WBGene00000908	F11A1.3	daf-12	ZF - NHR	ENSP00000342470	NR1H3	1, 2
WBGene00001062	R10D12.2	dpr-1	ZF - NHR			1
WBGene00001400	F56E3.4	fax-1	ZF - NHR	ENSP00000317199	NR2E3	1, 2
WBGene00003600	R09G11.2	nhr-1	ZF - NHR			1, 2
WBGene00003609	B0280.8	nhr-10	ZF - NHR			1, 2
WBGene00003690	C28D4.1	nhr-100	ZF - NHR			1
WBGene00003691	H12C20.6	nhr-101	ZF - NHR
WBGene00003692	T06C12.6	nhr-102	ZF - NHR			2
WBGene00003693	F44C8.4	nhr-103	ZF - NHR			1, 2
WBGene00003694	R11E3.5	nhr-104	ZF - NHR			1
WBGene00003695	C06G3.1	nhr-105	ZF - NHR			1, 2
WBGene00003696	T01G6.4	nhr-106	ZF - NHR			1
WBGene00003697	C33G8.11	nhr-107	ZF - NHR
WBGene00003698	F35E8.12	nhr-108	ZF - NHR			1, 2
WBGene00003699	T12C9.5	nhr-109	ZF - NHR
WBGene00003610	ZC410.1	nhr-11	ZF - NHR			1, 2
WBGene00003700	Y46H3D.5	nhr-110	ZF - NHR			2
WBGene00003701	F44G3.9	nhr-111	ZF - NHR			1, 2
WBGene00003702	Y70C5C.6	nhr-112	ZF - NHR			1
WBGene00003703	ZK1025.9	nhr-113	ZF - NHR			1, 2
WBGene00003704	Y45G5AM.1	nhr-114	ZF - NHR
WBGene00003705	T27B7.4	nhr-115	ZF - NHR			1
WBGene00003706	F09C6.9	nhr-116	ZF - NHR			1
WBGene00003707	F16B4.12	nhr-117	ZF - NHR			2
WBGene00003708	F13A2.8	nhr-118	ZF - NHR
WBGene00003709	K12H6.1	nhr-119	ZF - NHR			1, 2
WBGene00003611	R04B5.4	nhr-12	ZF - NHR			2
WBGene00003710	C25B8.6	nhr-120	ZF - NHR			1
WBGene00003711	E02H9.8	nhr-121	ZF - NHR			1, 2
WBGene00003712	Y41D4B.9	nhr-122	ZF - NHR
WBGene00003713	M02H5.7	nhr-123	ZF - NHR			1, 2
WBGene00003714	C17E7.8	nhr-124	ZF - NHR			1, 2
WBGene00003715	R02D1.1	nhr-125	ZF - NHR			1, 2
WBGene00003716	F44C8.10	nhr-126	ZF - NHR			1, 2
WBGene00003717	T13F3.3	nhr-127	ZF - NHR			1, 2
WBGene00003718	F44C8.5	nhr-128	ZF - NHR			1, 2
WBGene00003719	C50B6.14	nhr-129	ZF - NHR
WBGene00003612	Y5H2B.2	nhr-13	ZF - NHR			1, 2
WBGene00003720	T01G6.8	nhr-130	ZF - NHR			1, 2
WBGene00003721	T01G6.2	nhr-131	ZF - NHR
WBGene00003722	R11G11.1	nhr-132	ZF - NHR			1, 2
WBGene00003723	F44C8.8	nhr-133	ZF - NHR			2
WBGene00003724	F44C8.2	nhr-134	ZF - NHR			1, 2
WBGene00003726	C13C4.3	nhr-136	ZF - NHR			1
WBGene00003727	C56E10.4	nhr-137	ZF - NHR			1, 2
WBGene00003728	C28D4.9	nhr-138	ZF - NHR
WBGene00016365	C33G8.8	nhr-139	ZF - NHR			1, 2
WBGene00003613	T01B10.4	nhr-14	ZF - NHR	ENSP00000343807		1, 2
WBGene00016366	C33G8.9	nhr-140	ZF - NHR			1, 2
WBGene00017787	F25E5.6	nhr-141	ZF - NHR			1, 2
WBGene00018430	F44E7.8	nhr-142	ZF - NHR			1
WBGene00019116	F59E11.11	nhr-143	ZF - NHR			1, 2
WBGene00012703	Y39B6A.47	nhr-145	ZF - NHR
WBGene00045255	Y41D4B.27	nhr-146	ZF - NHR
WBGene00015395	C03G6.8	nhr-147	ZF - NHR			1, 2
WBGene00015396	C03G6.10	nhr-148	ZF - NHR			1, 2
WBGene00015397	C03G6.12	nhr-149	ZF - NHR			1
WBGene00003614	F33E11.1	nhr-15	ZF - NHR			1, 2
WBGene00007367	C06B8.1	nhr-150	ZF - NHR			1, 2
WBGene00015705	C12D5.2	nhr-152	ZF - NHR			1, 2
WBGene00007546	C13C4.1	nhr-153	ZF - NHR			1, 2
WBGene00007547	C13C4.2	nhr-154	ZF - NHR			1
WBGene00015758	C14C6.4	nhr-155	ZF - NHR			1
WBGene00015897	C17E7.1	nhr-156	ZF - NHR			1, 2
WBGene00015900	C17E7.5	nhr-157	ZF - NHR			1
WBGene00015901	C17E7.6	nhr-158	ZF - NHR			1
WBGene00015902	C17E7.7	nhr-159	ZF - NHR			1
WBGene00003615	T12C9.6	nhr-16	ZF - NHR			2
WBGene00016364	C33G8.7	nhr-161	ZF - NHR
WBGene00016367	C33G8.10	nhr-162	ZF - NHR			1, 2
WBGene00016368	C33G8.12	nhr-163	ZF - NHR			1, 2
WBGene00008056	C41G6.5	nhr-164	ZF - NHR			2
WBGene00008158	C47F8.2	nhr-165	ZF - NHR			1, 2
WBGene00016772	C49D10.2	nhr-166	ZF - NHR			1, 2
WBGene00008208	C49F5.4	nhr-167	ZF - NHR			1
WBGene00008221	C50B6.8	nhr-168	ZF - NHR			1
WBGene00008289	C54C8.1	nhr-169	ZF - NHR			1, 2
WBGene00003616	C02B4.2	nhr-17	ZF - NHR			1, 2
WBGene00008309	C54E10.5	nhr-170	ZF - NHR			1, 2
WBGene00016926	C54F6.8	nhr-171	ZF - NHR			1, 2
WBGene00016927	C54F6.9	nhr-172	ZF - NHR			1
WBGene00016975	C56E10.1	nhr-173	ZF - NHR			1
WBGene00008474	E03H4.6	nhr-174	ZF - NHR			1
WBGene00008630	F09F3.10	nhr-175	ZF - NHR			1
WBGene00008830	F14H3.11	nhr-176	ZF - NHR			1, 2
WBGene00017503	F16B4.1	nhr-177	ZF - NHR			2
WBGene00017510	F16B4.9	nhr-178	ZF - NHR			1, 2
WBGene00017512	F16B4.11	nhr-179	ZF - NHR			2
WBGene00003617	F44C8.3	nhr-18	ZF - NHR			1, 2
WBGene00017961	F31F4.12	nhr-180	ZF - NHR			1, 2
WBGene00018189	F38H12.3	nhr-181	ZF - NHR			1, 2
WBGene00018265	F41B5.9	nhr-182	ZF - NHR			1
WBGene00018266	F41B5.10	nhr-183	ZF - NHR			1, 2
WBGene00018415	F44C8.9	nhr-184	ZF - NHR			1, 2
WBGene00018539	F47C10.1	nhr-185	ZF - NHR			1, 2
WBGene00018541	F47C10.3	nhr-186	ZF - NHR			1, 2
WBGene00018542	F47C10.4	nhr-187	ZF - NHR			1, 2
WBGene00018544	F47C10.7	nhr-188	ZF - NHR			1, 2
WBGene00018545	F47C10.8	nhr-189	ZF - NHR
WBGene00003618	E02H1.7	nhr-19	ZF - NHR			1, 2
WBGene00018622	F48G7.11	nhr-190	ZF - NHR			1, 2
WBGene00010180	F57A8.5	nhr-192	ZF - NHR			1, 2
WBGene00010215	F57G8.6	nhr-193	ZF - NHR			1, 2
WBGene00019115	F59E11.10	nhr-195	ZF - NHR			1
WBGene00010600	K06B4.5	nhr-196	ZF - NHR			1, 2
WBGene00010602	K06B4.7	nhr-197	ZF - NHR			1, 2
WBGene00010603	K06B4.8	nhr-198	ZF - NHR			1, 2
WBGene00010604	K06B4.10	nhr-199	ZF - NHR			1, 2
WBGene00003601	C32F10.6	nhr-2	ZF - NHR			1, 2
WBGene00003619	F43C1.4	nhr-20	ZF - NHR			2
WBGene00019741	M02H5.3	nhr-201	ZF - NHR			1
WBGene00019742	M02H5.4	nhr-202	ZF - NHR
WBGene00019743	M02H5.5	nhr-203	ZF - NHR
WBGene00019816	R02C2.4	nhr-204	ZF - NHR			1
WBGene00011002	R04B5.3	nhr-205	ZF - NHR			1, 2
WBGene00011097	R07B7.13	nhr-206	ZF - NHR			1
WBGene00011098	R07B7.14	nhr-207	ZF - NHR			1, 2
WBGene00011099	R07B7.15	nhr-208	ZF - NHR			1, 2
WBGene00011100	R07B7.16	nhr-209	ZF - NHR			1
WBGene00003620	F21D12.1	nhr-21	ZF - NHR			1, 2
WBGene00020015	R11G11.12	nhr-210	ZF - NHR			1
WBGene00020152	T01G6.5	nhr-211	ZF - NHR			2
WBGene00020153	T01G6.6	nhr-212	ZF - NHR			1, 2
WBGene00011520	T06C12.13	nhr-213	ZF - NHR			1, 2
WBGene00011567	T07C5.4	nhr-215	ZF - NHR			1
WBGene00020385	T09D3.4	nhr-216	ZF - NHR			1, 2
WBGene00011651	T09E11.2	nhr-217	ZF - NHR			1
WBGene00011750	T13F3.2	nhr-218	ZF - NHR			1
WBGene00003621	K06A1.4	nhr-22	ZF - NHR			1, 2
WBGene00020591	T19H12.8	nhr-220	ZF - NHR			1, 2
WBGene00020748	T24A6.8	nhr-221	ZF - NHR			1
WBGene00020750	T24A6.11	nhr-222	ZF - NHR			1
WBGene00012050	T26E4.8	nhr-223	ZF - NHR			1
WBGene00020849	T27B7.2	nhr-225	ZF - NHR			1
WBGene00020850	T27B7.3	nhr-226	ZF - NHR			1, 2
WBGene00020851	T27B7.5	nhr-227	ZF - NHR			1
WBGene00020852	T27B7.6	nhr-228	ZF - NHR			2
WBGene00013795	Y116A8C.18	nhr-229	ZF - NHR			1
WBGene00003622	C01H6.5	nhr-23	ZF - NHR		RORB	1, 2
WBGene00012446	Y17D7A.1	nhr-230	ZF - NHR			1
WBGene00012449	Y17D7B.1	nhr-231	ZF - NHR			1, 2
WBGene00012494	Y22F5A.1	nhr-232	ZF - NHR			1, 2
WBGene00006471	Y32B12B.6	nhr-233	ZF - NHR			1
WBGene00012596	Y38E10A.18	nhr-234	ZF - NHR			2
WBGene00021417	Y38F2AL.5	nhr-236	ZF - NHR
WBGene00021610	Y46H3D.6	nhr-237	ZF - NHR			1, 2
WBGene00021611	Y46H3D.7	nhr-238	ZF - NHR
WBGene00021848	Y54F10AM.1	nhr-239	ZF - NHR
WBGene00013483	Y69H2.8	nhr-241	ZF - NHR
WBGene00022097	Y69A2AR.26	nhr-242	ZF - NHR			1
WBGene00013584	Y80D3A.4	nhr-243	ZF - NHR			2
WBGene00014189	ZK1025.10	nhr-245	ZF - NHR			2
WBGene00014193	ZK1037.5	nhr-247	ZF - NHR			1
WBGene00013940	ZK218.6	nhr-248	ZF - NHR			1
WBGene00003623	F11C1.6	nhr-25	ZF - NHR		NR5A2	1
WBGene00022755	ZK488.1	nhr-250	ZF - NHR			1
WBGene00022756	ZK488.4	nhr-251	ZF - NHR			1, 2
WBGene00022637	ZK6.2	nhr-252	ZF - NHR			1
WBGene00022639	ZK6.4	nhr-253	ZF - NHR			1, 2
WBGene00022640	ZK6.5	nhr-254	ZF - NHR			1
WBGene00014068	ZK678.2	nhr-255	ZF - NHR
WBGene00022805	ZK697.2	nhr-256	ZF - NHR			1, 2
WBGene00015869	C17A2.1	nhr-257	ZF - NHR			1, 2
WBGene00016126	C26B2.4	nhr-258	ZF - NHR			1, 2
WBGene00011568	T07C5.5	nhr-26	ZF - NHR			1
WBGene00016517	C38C3.9	nhr-260	ZF - NHR			1, 2
WBGene00016777	C49D10.9	nhr-261	ZF - NHR			1
WBGene00008619	F09C6.8	nhr-262	ZF - NHR			1
WBGene00008778	F14A5.1	nhr-264	ZF - NHR			1
WBGene00009608	F41D3.3	nhr-265	ZF - NHR			1
WBGene00018993	F56H1.2	nhr-266	ZF - NHR			1
WBGene00010410	H22D14.1	nhr-267	ZF - NHR			1, 2
WBGene00010601	K06B4.6	nhr-268	ZF - NHR			1
WBGene00011150	R08H2.9	nhr-269	ZF - NHR			1
WBGene00008901	F16H9.2	nhr-27	ZF - NHR			1
WBGene00020062	R13D11.8	nhr-270	ZF - NHR			1
WBGene00011396	T03E6.3	nhr-271	ZF - NHR			1, 2
WBGene00011565	T07C5.2	nhr-272	ZF - NHR			1
WBGene00020460	T12C9.1	nhr-273	ZF - NHR
WBGene00021522	Y41D4B.21	nhr-274	ZF - NHR
WBGene00021163	Y5H2A.2	nhr-275	ZF - NHR
WBGene00013512	Y71A12C.1	nhr-276	ZF - NHR			1
WBGene00022374	Y94H6A.1	nhr-277	ZF - NHR			2
WBGene00022636	ZK6.1	nhr-278	ZF - NHR			1
WBGene00003624	C11G6.4	nhr-28	ZF - NHR			2
WBGene00008884	F16B12.8	nhr-281	ZF - NHR			1, 2
WBGene00010186	F57A10.6	nhr-283	ZF - NHR
WBGene00012056	T26E4.16	nhr-285	ZF - NHR
WBGene00044699	VC5.6	nhr-286	ZF - NHR			1
WBGene00003602	H01A20.1	nhr-3	ZF - NHR			1, 2
WBGene00016091	C25E10.1	nhr-30	ZF - NHR			1
WBGene00003625	C26B2.3	nhr-31	ZF - NHR			1, 2
WBGene00003626	K08H2.8	nhr-32	ZF - NHR			2
WBGene00013976	ZK455.6	nhr-33	ZF - NHR			1
WBGene00003627	F58G6.5	nhr-34	ZF - NHR			2
WBGene00003628	C07A12.3	nhr-35	ZF - NHR	ENSP00000346339	HNF4G	1, 2
WBGene00017198	F07C3.10	nhr-36	ZF - NHR
WBGene00018412	F44C4.2	nhr-37	ZF - NHR			1, 2
WBGene00003629	K01H12.3	nhr-38	ZF - NHR			1, 2
WBGene00018404	F44A2.4	nhr-39	ZF - NHR			1
WBGene00003603	F32B6.1	nhr-4	ZF - NHR			1, 2
WBGene00003630	T03G6.2	nhr-40	ZF - NHR			2
WBGene00022423	Y104H12A.1	nhr-41	ZF - NHR	ENSP00000333275		1
WBGene00003632	C33G8.6	nhr-42	ZF - NHR			1, 2
WBGene00003633	C29E6.5	nhr-43	ZF - NHR			1, 2
WBGene00003634	T19A5.4	nhr-44	ZF - NHR			1
WBGene00003635	F16H11.5	nhr-45	ZF - NHR			1
WBGene00003636	C45E5.6	nhr-46	ZF - NHR			1, 2
WBGene00003637	C24G6.4	nhr-47	ZF - NHR			1, 2
WBGene00003638	ZK662.3	nhr-48	ZF - NHR
WBGene00003639	K10C3.6	nhr-49	ZF - NHR	ENSP00000346339	HNF4G	1, 2
WBGene00003604	Y73F8A.21	nhr-5	ZF - NHR
WBGene00003640	C06C6.5	nhr-50	ZF - NHR			1, 2
WBGene00003641	K06B4.1	nhr-51	ZF - NHR			1
WBGene00003642	K06B4.2	nhr-52	ZF - NHR
WBGene00003643	K06B4.11	nhr-53	ZF - NHR			2
WBGene00003644	F36D3.2	nhr-54	ZF - NHR			1, 2
WBGene00003645	T01G6.7	nhr-55	ZF - NHR			1
WBGene00003646	F44C8.6	nhr-56	ZF - NHR			1, 2
WBGene00003647	T05B4.2	nhr-57	ZF - NHR			1, 2
WBGene00003648	R11G11.2	nhr-58	ZF - NHR			1, 2
WBGene00003649	T27B7.1	nhr-59	ZF - NHR			1, 2
WBGene00003605	C48D5.1	nhr-6	ZF - NHR	ENSP00000344479	NR4A2	1, 2
WBGene00003650	F57A10.5	nhr-60	ZF - NHR			1, 2
WBGene00003651	W01D2.2	nhr-61	ZF - NHR			1
WBGene00003652	Y67A6A.2	nhr-62	ZF - NHR			1, 2
WBGene00003653	C06C6.4	nhr-63	ZF - NHR			1, 2
WBGene00003654	C45E1.1	nhr-64	ZF - NHR	ENSP00000312987	HNF4A	1
WBGene00003655	Y17D7A.3	nhr-65	ZF - NHR			1, 2
WBGene00003656	T09A12.4	nhr-66	ZF - NHR			1
WBGene00003657	C08F8.8	nhr-67	ZF - NHR	ENSP00000230083	NR2E1	1, 2
WBGene00003658	H12C20.3	nhr-68	ZF - NHR			1, 2
WBGene00003659	T23H4.2	nhr-69	ZF - NHR	ENSP00000343807		1, 2
WBGene00003606	F54D1.4	nhr-7	ZF - NHR			1, 2
WBGene00003660	Y51A2D.17	nhr-70	ZF - NHR			1, 2
WBGene00003661	K11E4.5	nhr-71	ZF - NHR			1, 2
WBGene00003662	C17A2.8	nhr-72	ZF - NHR			1, 2
WBGene00003663	C27C7.4	nhr-73	ZF - NHR			2
WBGene00003664	C27C7.3	nhr-74	ZF - NHR			1, 2
WBGene00003665	C49D10.6	nhr-75	ZF - NHR			1, 2
WBGene00015497	C05G6.1	nhr-76	ZF - NHR			1, 2
WBGene00003667	T15D6.6	nhr-77	ZF - NHR			1
WBGene00003668	F36A4.14	nhr-78	ZF - NHR			1
WBGene00003669	T26H2.9	nhr-79	ZF - NHR			2
WBGene00003607	F33D4.1	nhr-8	ZF - NHR	ENSP00000229022	VDR	1, 2
WBGene00003670	H10E21.3	nhr-80	ZF - NHR			1, 2
WBGene00003671	C47F8.8	nhr-81	ZF - NHR			1, 2
WBGene00003672	F41D3.1	nhr-82	ZF - NHR			1, 2
WBGene00003673	F48G7.3	nhr-83	ZF - NHR			1
WBGene00003674	T06C12.7	nhr-84	ZF - NHR			1, 2
WBGene00003675	W05B5.3	nhr-85	ZF - NHR	ENSP00000310006	NR1D2	1, 2
WBGene00003676	Y40B10A.8	nhr-86	ZF - NHR
WBGene00003677	Y41D4B.7	nhr-87	ZF - NHR			1
WBGene00003678	K08A2.5	nhr-88	ZF - NHR			1, 2
WBGene00003679	E03H4.13	nhr-89	ZF - NHR			1
WBGene00003608	ZK418.1	nhr-9	ZF - NHR			1, 2
WBGene00003680	ZK488.2	nhr-90	ZF - NHR			1, 2
WBGene00003681	Y15E3A.1	nhr-91	ZF - NHR	ENSP00000341135	NR6A1	1, 2
WBGene00003682	Y41D4B.8	nhr-92	ZF - NHR			1
WBGene00003684	C12D5.8	nhr-94	ZF - NHR			1
WBGene00003685	Y39B6A.17	nhr-95	ZF - NHR			1, 2
WBGene00003686	F44C8.11	nhr-96	ZF - NHR			1, 2
WBGene00003687	H27C11.1	nhr-97	ZF - NHR			1, 2
WBGene00003688	M02H5.6	nhr-98	ZF - NHR			1, 2
WBGene00003689	M02H5.1	nhr-99	ZF - NHR			2
WBGene00003854	T18D3.2	odr-7	ZF - NHR			1, 2
WBGene00004786	F44A6.2	sex-1	ZF - NHR	ENSP00000246672	NR1D1	1, 2
WBGene00016233	C29G2.5	srt-58	ZF - NHR			1
WBGene00006790	F55D12.4	unc-55	ZF - NHR	ENSP00000325819	NR2F1	1
WBGene00045515	ZK1037.13	ZK1037.13	ZF - NHR			1
WBGene00003725	VC5.5	nhr-135	ZF - NHR - 2 domains
WBGene00020555	T19A5.5	nhr-219	ZF - NHR - 2 domains			1
WBGene00015147	B0336.7	B0336.7	ZF - THAP			1, 2
WBGene00000383	C17G10.4	cdc-14	ZF - THAP	ENSP00000354916		1, 2
WBGene00006424	F49E10.5	ctbp-1	ZF - THAP	ENSP00000311825		1
WBGene00013055	Y50E8A.12	Y50E8A.12	ZF - THAP

RNAi feeding clones exist in the Ahringer library (1) or ORFeome 1.1 library (2) available from Source Bioscience and Open Biosystems

5.2 Transcription Factor Families

C. elegans contains representatives of most major transcription factor families found in other animals (Tables 1 and 2), and 344 (37%) of the C. elegans transcription factor genes have been matched with clear human orthologs by reciprocal BLAST analysis or using orthology prediction programs (Table 1) (Reece-Hoyes et al., 2005; PMID 16420670; Shaye and Greenwald, 2011; PMID 21647448). Interestingly, some families of DNA-binding domains seem more highly conserved during animal evolution than others (Figure 4). For example, 19 out of 19 (100%) MYB-like factors and 30 out of 41 bHLH factors (73%) have human orthologs. In comparison, only 6 out of 22 T-box genes (28%) and 0 out of 9 MADF-family genes (0%) have been conserved. As has been noted previously (Reece-Hoyes et al., 2005; PMID 16420670; Sluder et al., 1999; PMID 10022975), the number of likely nuclear hormone receptors (NHRs) has expanded greatly in C. elegans (272 members in Table 2) relative to humans (46 members; IPR001628; (Vaquerizas et al., 2009; PMID 19274049)).

DNA-binding Domain	Total members
ZF - NHR	272
ZF - C2H2	217
HD	101
bHLH	41
novel	34
bZIP	33
AT Hook	29
T-box	22
MYB	19
WH - Fork Head	18
HMG box	16
ZF - GATA	14
MADF	11
ZF - DM	11
WH - ETS	10
CBF	9
ZF - BED	9
HTH	7
MH1	7
Paired Domain	7
ZF - THAP	6
ARID/BRIGHT	5
COLD BOX	5
AP-2	4
SAND	4
WH - TDP	4
ZF - FLYWCH	4
IPT/TIG	3
p53	3
TSC-22/dip/bun	3
WH - HSF	3
Brinker	2
GC-rich DNA-binding domain	2
MADS box	2
PUR	2
WH	2
ZF - NF-X1 - 10 domains	2
CP2	1
p66 family	1
RNT	1
RPEL	1
STAT	1
TEA/ATTS	1
TRAP230 family	1
WH - DAC	1
WH - RFX	1
YL1 TF	1
ZF - C2CH	1
ZF - C2HC	1

Figure 4. C. elegans transcription factor genes with clear orthologs in the human genome.

The percentage of C. elegans genes from each DNA-binding domain family with clear orthologs in the human genome (Reece-Hoyes et al., 2005; PMID 16420670; Shaye and Greenwald, 2011; PMID 21647448). Only DNA-binding domain families with 3 or more C. elegans members are included.

5.3 Interspecies Comparisons

Genome sequencing of additional Caenorhabditis species allows a comparison of the C. elegans transcription factor gene family to those in other species (Haerty et al., 2008; PMID 18752680). C. briggsae and C. remanei contain similar numbers of transcription factor genes to C. elegans, and approximately 72% of the C. elegans transcription factor genes have detectable orthologs in both C. briggsae and C. remanei. This proportion of orthology is higher than that found overall for protein coding genes, suggesting transcription factor genes are under strong selective pressure. Transcription factor genes are not uniformly distributed on the chromosomes in C. elegans or C. briggsae, and many genes are located in clusters that are enriched for transcription factor genes compared to non-transcription factor genes. Furthermore members of gene families such as NHR, HOX, and T-box are frequently clustered in tandem arrays (Haerty et al., 2008; PMID 18752680).

5.4 Transcription Factor Targets

A major goal in studying transcription is to make the link between transcription factors and their target genes. These links have traditionally been made by identifying binding sites in experimentally verified targets of transcription factors by detailed promoter analyses. While this approach is still valuable, more recent techniques such as PCR based binding site selection, microarray analyses, yeast one-hybrid screens, and chromatin immunoprecipitation (ChIP) assays have expanded our ability to identify transcription factor binding sites and candidate target genes on a genome-wide scale (e.g., (Deplancke et al., 2006; PMID 16777607; McElwee et al., 2003; PMID 12882324; Niu et al., 2011; PMID 21177963; Zhong et al., 2010; PMID 20174564)). Our knowledge of transcription factor binding site specificity will continue to increase, but we provide references to find information about DNA binding site specificity and potential target genes for some C. elegans transcription factors (Table 3). As described more fully below (see Systematic genome-scale analysis of transcription regulation), data from many of these ChIP analyses is available at modENCODE.org and through WormBase.org. Likewise candidate transcription factor binding sites predicted from published data and user generated position weight matrices can be visualized in the Genome Browser at WormBase.org and modENCODE.org by accessing the Sequence Motif track.

Gene WB ID	Sequence Name Gene	Gene Public Name	Target genes	References for C. elegans transcription factor targets and binding site data
WBGene00000096	C41G7.5	ahr-1	in vitro binding	(Powell-Coffman et al., 1998; PMID 9501178)
WBGene00044330	R08B4.2	alr-1	ChIP, ceh-23, F55B11.4, lbp-8, mir-77	(Niu et al., 2011; PMID 21177963; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00019424	K06A1.1	aptf-1	dac-1, ech-6, fat-2, H32C10.3, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00020368	T08H4.3	ast-1	cat-2, cat-4, dat-1, cat-1, bas-1, M01D1.2, tra-1	(Deplancke et al., 2006; PMID 16777607; Flames and Hobert, 2009; PMID 19287374)
WBGene00000220	K08F8.2	atf-2	lin-48	(Wang et al., 2006; PMID 16310763)
WBGene00000223	C07G2.2	atf-7	unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00008081	C44B9.4	athp-1	daf-3, pop-1, acs-11, ceh-23, cog-1, dac-1, ech-6, egg-2, elo-2, F55B11.4, fat-2, nhr-86, unc-86, vha-15, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00013799	Y116A8C.22	athp-3	mir-243	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00015075	B0238.11	B0238.11	lin-4	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00012943	Y47D3B.9	bed-2	nhr-28, acs-11, cyp-35A3, egg-2, vha-15, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003847	F25D7.3	blmp-1	ChIP	(Niu et al., 2011; PMID 21177963)
WBGene00045215	C02F12.10	C02F12.10	F55B11.4, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00016310	C32D5.1	C32D5.1	acs-11, C15C7.5, ceh-23, cog-1, cyp-35A3, dac-1, daf-12, ech-6, egg-2, elo-2, elt-4, F55B11.4, far-7, fat-2, fat-4, nhr-137, nhr-178, nhr-86, T23F11.4, unc-86, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00016712	C46E10.8	C46E10.8	fat-2, mir-243	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00016725	C46H3.2	C46H3.2	mir-77	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000428	F16H11.4	ceh-1	acs-11, ceh-23, cog-1, cyp-35A5, dac-1, elt-4, F55B11.4, lbp-8, nhr-178, nhr-68, nhr-86, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000435	W03A3.1	ceh-10	ceh-23 and 38 other AIY terminal genes, acs-11, C15C7.5, ech-6, elo-2, nhr-68	(Wenick and Hobert, 2004; PMID 15177025; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000438	F46C8.5	ceh-14	ChIP, K07D4.6, acs-11, ceh-23, cog-1, dac-1, ech-6, F55B11.4, fat-2, nhr-178, vha-15, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Niu et al., 2011; PMID 21177963; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000440	D1007.1	ceh-17	daf-3, C15C7.5, ceh-23, cog-1, dac-1, ech-6, F55B11.4, gpd-3, lbp-8, mir-243, mir-77, nhr-68, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000441	ZC64.3	ceh-18	elo-2	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000442	F20D12.6	ceh-19	cog-1, hlh-15, lbp-8	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000443	F31E3.1	ceh-20	mls-2, psa-3, hlh-8, W01C9.1, acs-11, C06E7.3, F59F5.2, nhr-178, T23F11.4, vha-15	(Arata et al., 2006; PMID 16824957; Deplancke et al., 2006; PMID 16777607; Jiang et al., 2008; PMID 18316179; Liu and Fire, 2000; PMID 11060243; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000445	F29F11.5	ceh-22	myo-2, ceh-22	(Berger et al., 2006; PMID 16998473; Kuchenthal et al., 2001; PMID 11783006; Okkema and Fire, 1994; PMID 7925019)
WBGene00000451	C33D12.7	ceh-30	ChIP, ceh-23, cog-1, cyp-35A5, elt-4, hlh-15, nhr-68, vha-15	(Niu et al., 2011; PMID 21177963; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000452	C33D12.1	ceh-31	acs-11, ceh-23, cog-1, cyp-35A5, ech-6, elt-4, F55B11.4, hlh-15, lbp-8, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000455	C10G8.6	ceh-34	egl-1, pqn-60	(Deplancke et al., 2006; PMID 16777607; Hirose et al., 2010; PMID 20713707)
WBGene00000457	C37E2.4	ceh-36	ceh-23	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000458	C37E2.5	ceh-37	ceh-23, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000459	F22D3.1	ceh-38	elt-4, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000460	T26C11.7	ceh-39	nhr-86, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000463	C28A5.4	ceh-43	elt-4, ceh-23, cog-1, cyp-35A5, dac-1, elt-4, F55B11.4, lbp-8, nhr-178, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00022837	ZK993.1	ceh-45	ceh-23, mir-243, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00015934	C17H12.9	ceh-48	sma-3, ztf-4, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00017538	F17A9.6	ceh-49	F38B6.1	(Deplancke et al., 2006; PMID 16777607)
WBGene00013583	Y80D3A.3	ceh-51	unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00020485	T13C5.4	ceh-54	ech-6	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00007417	C07E3.6	ceh-58	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000431	K02B12.1	ceh-6	aqp-8, acs-11, ceh-23, ech-6, egg-2, elo-2, lbp-8	(Mah et al., 2007; PMID 17660295; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00011069	R06F6.6	ceh-62	acs-11, ceh-23, cog-1, cyp-35A5, dac-1, elt-4, F55B11.4, fat-2, lbp-8, nhr-178, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000433	ZK265.4	ceh-8	M01D1.2, acdh-1, C15C7.5, ceh-23, cog-1, dac-1, ech-6, egg-2, F55B11.4, far-7, hlh-15, lbp-8, nhr-178, vha-15, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000434	Y65B4BR.9	ceh-9	ceh-23, cog-1, cyp-35A5, elt-4, F55B11.4, lbp-8, nhr-68, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00019864	R04A9.5	ceh-93	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000468	F43G9.11	ces-1	egl-1, B0507.1, ztf-4, C30F12.1	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2009; PMID 19372275; Thellmann et al., 2003; PMID 12874127; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000469	ZK909.4	ces-2	ces-1, lin-48	(Metzstein and Horvitz, 1999; PMID 10518212; Wang et al., 2006; PMID 16310763)
WBGene00000473	F46F11.2	cey-2	die-1, F09F3.6	(Deplancke et al., 2006; PMID 16777607)
WBGene00000476	T23D8.8	cfi-1	in vitro binding, K07D4.6, cog-1, F55B11.4	(Deplancke et al., 2006; PMID 16777607; Shaham and Bargmann, 2002; PMID 11959845; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000483	C55B7.12	che-1	cog-1, gcy-5, gcy-7, lim-6, lsy-6, ceh-36	(Chang et al., 2003; PMID 12952888; Etchberger et al., 2009; PMID 19060335; O'Meara et al., 2009; PMID 19189954)
WBGene00000561	C34E10.7	cnd-1	PBM	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181)
WBGene00000584	R03C1.3	cog-1	cyp-35A5, F55B11.4, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000793	Y41C4A.4	crh-1	T23G5.3	(Deplancke et al., 2006; PMID 16777607)
WBGene00008386	D1081.8	D1081.8	mir-243	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000895	B0412.1	dac-1	acs-11, C30F12.1, ceh-23, cog-1, cyp-35A3, dac-1, elo-2, F55B11.4, F59F5.2, fat-2, nhr-86, T23F11.4, unc-86, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000908	F11A1.3	daf-12	ceh-22, myo-2, many others, in vitro binding	(Ao et al., 2004; PMID 15375261; Shostak et al., 2004; PMID 15489294)
WBGene00000912	R13H8.1	daf-16	ChIP	(Furuyama et al., 2000; PMID 10880363; Lee et al., 2003; PMID 12690206; McElwee et al., 2003; PMID 12882324; Oh et al., 2006; PMID 16380712)
WBGene00000914	F33H1.1	daf-19	xbx-1, nph-1, nph-4, daf-19	(Deplancke et al., 2006; PMID 16777607; Schafer et al., 2003; PMID 12802075; Winkelbauer et al., 2005; PMID 16291722)
WBGene00000899	F25E2.5	daf-3	myo-2, mdl-3, mdl-1, dhs-25, his-14, lin-4, lpd-2, nhr-86, T23F11.4	(Deplancke et al., 2006; PMID 16777607; Thatcher et al., 1999; PMID 9834189; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00000904	R05D11.1	daf-8	nhr-68, T23G5.3	(Deplancke et al., 2006; PMID 16777607)
WBGene00000995	C18D1.1	die-1	bar-1, C04F12.9, C18A11.1, ceh-13, daf-3, emb-5, F25E5.2, fat-5, ges-1, inx-6, K07D4.6, lin-48, mab-23, nhr-28, nhr-68, pos-1, pqn-26, R06F6.6, sma-3, T14G10.4, T22H9.4, tra-1, W06F12.3, Y38H6C.14, Y49E10.4, zag-1, ztf-4, acs-11, C15C7.5, ceh-23, cog-1, cyp-35A3, dac-1, daf-12, ech-6, egg-2, elo-2, elt-4, F55B11.4, fat-2, fat-6, lin-4, mir-243, nhr-137, nhr-178, nhr-68, nhr-86, T23F11.4, unc-86, vha-15, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00007929	C34D1.1	dmd-10	elt-4, F55B11.4, nhr-68, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00012832	Y43F8C.10	dmd-3	ceh-23, egg-2, elt-4, F55B11.4	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00007776	C27C12.6	dmd-4	elt-4, sma-3, acs-11, ceh-23, cog-1, dac-1, ech-6, egg-2, F55B11.4, fat-2, unc-86, vha-15, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00017326	F10C1.5	dmd-5	elt-4, acs-11, ceh-23, cog-1, dac-1, ech-6, egg-2, elt-4, F55B11.4, fat-2, lin-4, mir-243, unc-86, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00007058	F13G11.1	dmd-6	acs-11, cog-1, fat-2, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00019521	K08B12.2	dmd-7	gpd-3	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00020708	T22H9.4	dmd-8	ceh-23	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001029	F38A5.13	dnj-11	lin-4	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001079	T22B3.1	dpy-20	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00009584	F40F9.7	drap-1	cog-1, fat-2	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001096	C18B12.3	dsc-1	C15C7.5, T23F11.4, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001155	T05G5.6	ech-6	C04F12.9	(Deplancke et al., 2006; PMID 16777607)
WBGene00001186	F55A8.1	egl-18	elt-4	(Deplancke et al., 2006; PMID 16777607)
WBGene00001194	C04A2.3	egl-27	ChIP	(Niu et al., 2011; PMID 21177963)
WBGene00001204	C04G2.7	egl-38	lin-48, in vitro binding	(Johnson et al., 2001; PMID 11532910; Zhang et al., 2005; PMID 15923112)
WBGene00001208	F28B12.2	egl-44	C04F12.9, fat-5, lin-48, M01D1.2, med-2, nhr-28, acs-11, C30F12.1, dac-1, fat-2, fat-4, mir-243, nhr-8, opt-2, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001174	C08C3.1	egl-5	ChIP, acs-11, ceh-23, cog-1, cyp-35A5, dac-1, elt-4, F55B11.4, fat-2, hlh-15, lbp-8, nhr-68, nhr-86, Y57A10A.27	(Niu et al., 2011; PMID 21177963; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001249	W09C2.1	elt-1	bioinformatics, msp-113, ceh-13, peb-1, far-7, mir-77	(del Castillo-Olivares et al., 2009; PMID 19591818; Deplancke et al., 2006; PMID 16777607; Shim, 1999; PMID 10597043; Shim et al., 1995; PMID 7473742; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001250	C33D3.1	elt-2	SAGE, ref-1, ges-1, pho-1, mtl-1, mtl-2, ceh-13, elt-4, ges-1, peb-1, elt-4, F55B11.4, mir-77, nhr-8	(Deplancke et al., 2006; PMID 16777607; Egan et al., 1995; PMID 7649372; Fukushige et al., 2005; PMID 15733671; McGhee et al., 2007; PMID 17113066; Moilanen et al., 1999; PMID 10514435; Neves et al., 2007; PMID 18003741; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001251	K02B9.4	elt-3	ChIP, ceh-13, elt-4, ges-1, peb-1, elt-4, F55B11.4, mir-77	(Deplancke et al., 2006; PMID 16777607; Niu et al., 2011; PMID 21177963; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001252	C39B10.6	elt-4	mir-243	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001253	F52C12.5	elt-6	elt-4, F55B11.4, mir-77, nhr-178	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00015981	C18G1.2	elt-7	elt-4, F55B11.4, mir-77	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001310	F58E10.2	end-1	in vitro binding, exp-2, mir-77	(Deplancke et al., 2006; PMID 16777607; Shoichet et al., 2000; PMID 10760276; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001311	F58E10.5	end-3	ceh-13, ges-1, mir-77	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001324	R11E3.6	eor-1	ChIP	(Niu et al., 2011; PMID 21177963)
WBGene00017687	F22A3.1	ets-4	mab-23	(Deplancke et al., 2006; PMID 16777607)
WBGene00016600	C42D8.4	ets-5	B0507.1, bar-1, pqn-67, tra-1, inx-6	(Deplancke et al., 2006; PMID 16777607)
WBGene00001377	C49A1.4	eya-1	unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00013147	Y53C12C.1	eyg-1	nhr-178	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00008587	F08G12.3	F08G12.3	dac-1, F59F5.2, gpd-3, mdt-15, unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00008640	F10B5.3	F10B5.3	mir-243, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00009174	F26H9.2	F26H9.2	mir-77, nhr-86, opt-2	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00009827	F47G4.6	F47G4.6	C49C3.5	(Deplancke et al., 2006; PMID 16777607)
WBGene00001400	F56E3.4	fax-1	in vitro binding	(DeMeo et al., 2008; PMID 18179707)
WBGene00001436	C29F7.5	fkh-4	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001438	B0286.5	fkh-6	elt-4, F55B11.4, nhr-68, unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001440	F40H3.4	fkh-8	C18A11.1	(Deplancke et al., 2006; PMID 16777607)
WBGene00012435	Y11D7A.12	flh-1	lin-4, mir-241, mir-48, mir-53, mir-59, and mir-358-357	(Ow et al., 2008; PMID 18794349; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00016138	C26E6.2	flh-2	lin-4	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001345	F29G9.4	fos-1	egl-13	(Oommen and Newman, 2007; PMID 17942488)
WBGene00010453	K01B6.1	fozi-1	acs-11, unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001568	F32H2.1	gei-11	ChIP	(Niu et al., 2011; PMID 21177963)
WBGene00008092	C44F1.2	gmeb-3	mir-243, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00007732	C25G4.4	gmeb-4	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001707	Y48G8AR.1	grh-1	dbl-1, mab-5, pcn-1	(Venkatesan et al., 2003; PMID 12888489)
WBGene00010353	H02I12.5	H02I12.5	C30G12.1, ceh-13, dpr-1, nhr-28, hlh-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001824	F13D11.2	hbl-1	let-7	(Roush and Slack, 2009; PMID 19627983)
WBGene00001948	B0304.1	hlh-1	ChIP, PBM	(Blackwell et al., 1994; PMID 7939715; De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181; Krause et al., 1992; PMID 1338434; Lei et al., 2010; PMID 21209968; Niu et al., 2011; PMID 21177963)
WBGene00001954	ZK682.4	hlh-10	PBM	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181)
WBGene00001955	F58A4.7	hlh-11	PBM	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181)
WBGene00001958	C18A3.8	hlh-14	PBM	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181)
WBGene00001959	C43H6.8	hlh-15	PBM	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181)
WBGene00001962	F57C12.3	hlh-19	PBM	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181)
WBGene00001949	M05B5.5	hlh-2	lin-3, egl-1, lag-2	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181; Hwang and Sternberg, 2004; PMID 14660442; Karp and Greenwald, 2003; PMID 14701877; Thellmann et al., 2003; PMID 12874127)
WBGene00001964	C17C3.7	hlh-25	PBM	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181)
WBGene00001965	C17C3.8	hlh-26	PBM	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181)
WBGene00001966	C17C3.10	hlh-27	PBM, gpd-3, lin-4	(Grove et al., 2009; PMID 196321817; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001968	F31A3.4	hlh-29	PBM	(Grove et al., 2009; PMID 19632181)
WBGene00001950	T24B8.6	hlh-3	egl-1, PBM	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181; Krause et al., 1997; PMID 9187144; Thellmann et al., 2003; PMID 12874127)
WBGene00020930	W02C12.3	hlh-30	PBM, mir-243	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001951	T05G5.2	hlh-4	PBM	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181)
WBGene00001953	C02B8.4	hlh-8	arg-1, ceh-24, egl-15, mls-1	(Corsi et al., 2000; PMID 10769229; De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181; Harfe and Fire, 1998; PMID 9425137; Harfe et al., 1998; PMID 9716413; Kostas and Fire, 2002; PMID 11799068; Zhao et al., 2007; PMID 17369030)
WBGene00018786	F54A5.1	hmbx-1	nhr-8	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001971	Y48B6A.14	hmg-1.1	F52B11.5, sma-3	(Deplancke et al., 2006; PMID 16777607)
WBGene00001976	T05A7.4	hmg-11	unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00002004	Y53C10A.12	hsf-1	in vitro binding	(Enoki and Sakurai, 2011; PMID 21510947)
WBGene00007984	C36F7.1	irx-1	inx-6	(Deplancke et al., 2006; PMID 16777607)
WBGene00012005	T24H10.7	jun-1	egl-13	(Oommen and Newman, 2007; PMID 17942488)
WBGene00002245	K08B4.1	lag-1	hlh-6, ref-1	(Christensen et al., 1996; PMID 8625826; Ghai and Gaudet, 2008; PMID 18706403; Neves et al., 2007; PMID 18003741)
WBGene00002601	F26B1.7	let-381	ceh-34, F55B11.4	(Amin et al., 2010; PMID 20335356; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00002990	C37F5.1	lin-1	lin-39, T23F11.4	(Miley et al., 2004; PMID 15342509; Wagmaister et al., 2006; PMID 16782085; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003000	ZC247.3	lin-11	ChIP, acs-11, cog-1, dac-1, F55B11.4, nhr-178, vha-15, Y57A10A.27	(Niu et al., 2011; PMID 21177963; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003002	C03B8.4	lin-13	ChIP	(Niu et al., 2011; PMID 21177963)
WBGene00003003	T25C12.1	lin-14	ins-33	(Hristova et al., 2005; PMID 16314527)
WBGene00023497	ZK662.4	lin-15B	ChIP	(Niu et al., 2011; PMID 21177963)
WBGene00003012	F18A1.2	lin-26	hlh-6, inx-6, lin-48, M01D1.2, tra-1, gpd-3, hlh-15, mir-77, ref-2	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003015	W03C9.4	lin-29	col-19	(Rougvie and Ambros, 1995; PMID 7671813)
WBGene00003018	T14F9.5	lin-32	PBM	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181)
WBGene00003024	C07H6.7	lin-39	hlh-8, egl-17, egl-18/elt-5, elt-6, possible direct repressor of eff-1, cog-1, dac-1, elt-4, F55B11.4, nhr-86, Y57A10A.27	(Cui and Han, 2003; PMID 12710960; Koh et al., 2002; PMID 12399309; Liu and Fire, 2000; PMID 11060243; Niu et al., 2011; PMID 21177963; Shemer and Podbilewicz, 2002; PMID 12502736; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003033	F34D10.5	lin-48	B0507.1	(Deplancke et al., 2006; PMID 16777607)
WBGene00003037	JC8.6	lin-54	ChIP, ceh-2, dpr-1, ets-4, ges-1, inx-6, K07D4.6, nhr-68, pos-1, tra-1, Y38H6C.14, ztf-4, acs-11, ceh-23, cyp-35A3, cyp-35A5, ech-6, egg-2, elo-2, F55B11.4, fat-6, nhr-137, nhr-68, T23F11.4, unc-86, vha-15, ztf-27	(Deplancke et al., 2006; PMID 16777607; Tabuchi et al., 2011; PMID 21589891; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003044	F18A1.3	lir-1	sma-3, gpd-3	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00009937	F52F12.4	lsl-1	T23G5.3, mir-243	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003087	F49H12.1	lsy-2	T23G5.3, daf-12, mir-243, unc-86	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003114	C32C4.5	mab-23	K07D4.6	(Deplancke et al., 2006; PMID 16777607)
WBGene00003100	Y53C12B.5	mab-3	vit-2, other vits, nhr-178	(Yi and Zarkower, 1999; PMID 9927589; Reece-Hoyes et al., 2011; PMID 2203770)
WBGene00003102	C08C3.3	mab-5	ChIP, elt-4, pop-1, acs-11, C06E7.3, ceh-23, cog-1, elt-4, F55B11.4, fat-2, lbp-8, nhr-178, nhr-86, vha-15, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Niu et al., 2011; PMID 21177963; Reece-Hoyes et al., 2011; PMID 2203770)
WBGene00021942	Y55F3BR.5	madf-1	acs-11, cog-1, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00011315	T01C1.2	mbr-1	fat-2	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003163	R03E9.1	mdl-1	ChIP	(De Masi et al., 2011; PMID 21335608; Grove et al., 2009; PMID 19632181; Niu et al., 2011; PMID 21177963)
WBGene00003167	F01D4.6	mec-3	mec-4, mec-7, see also UNC-86, fat-2, vha-15	(Duggan et al., 1998; PMID 9735371; Way and Chalfie, 1988; PMID 2898300; Reece-Hoyes et al., 2011; PMID 2203770)
WBGene00003180	T24D3.1	med-1	end-1, end-3	(Broitman-Maduro et al., 2005; PMID 15737937)
WBGene00003182	W10D5.1	mef-2	str-1	(Choi et al., 2002; PMID 12054517; Dichoso et al., 2000; PMID 10882527; van der Linden et al., 2007; PMID 17170704)
WBGene00003218	M04B2.1	mep-1	ChIP, dac-1	(Niu et al., 2011; PMID 21177963; Reece-Hoyes et al., 2011; PMID 2203770)
WBGene00003241	T05C12.6	mig-5	acs-11, acs-2, C30F12.1, ceh-23, cog-1, dac-1, daf-12, ech-6, egg-2, elo-2, elt-4, far-7, fat-2, fat-4, H32C10.3, hlh-15, lin-4, mdt-15, mir-243, nhr-86, opt-2, T23F11.4, unc-86, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003377	C39E6.4	mls-2	elt-4, K07D4.6, acs-11, ceh-23, cog-1, cyp-35A3, cyp-35A5, dac-1, ech-6, egg-2, elo-2, elt-4, F55B11.4, F59F5.2, fat-2, fat-7, hlh-15, lbp-8, nhr-178, nhr-68, nhr-86, tag-257, vha-15, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003509	T19B10.11	mxl-1	bioinformatics	(De Masi et al., 2011; PMID 21335608)
WBGene00003510	F40G9.11	mxl-2	F25E5.2	(Deplancke et al., 2006; PMID 16777607)
WBGene00003511	F46G10.6	mxl-3	bioinformatics, mir-243	(De Masi et al., 2011; PMID 21335608; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003592	ZK1290.4	nfi-1	in vitro binding, in vitro binding, cog-1, dac-1, fat-2, nhr-86, unc-86, vha-15	(Lazakovitch et al., 2005; PMID 16242019; Whittle et al., 2009; PMID 19584245; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003600	R09G11.2	nhr-1	ceh-23, dhs-25, elt-4, nhr-137, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003609	B0280.8	nhr-10	T14G10.4, acdh-1, dhs-25, elt-4, fat-4, gpd-3, nhr-137, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003692	T06C12.6	nhr-102	dhs-25, mir-243, nhr-178, nhr-8, ref-2	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003695	C06G3.1	nhr-105	dac-1, elt-4, F55B11.4, fat-2, mir-243, unc-86, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003699	T12C9.5	nhr-109	C04F12.9, nhr-178, nhr-86, ref-2	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003610	ZC410.1	nhr-11	nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003701	F44G3.9	nhr-111	bar-1, elo-6, ets-4, exp-2, inx-6, mab-23, sma-3, ZK682.5, dhs-25, egg-2, F59F5.2, gpd-3, mdt-15, mir-243, nhr-178, nhr-68, nhr-8, nhr-86, unc-86, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003611	R04B5.4	nhr-12	nhr-178, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003728	C28D4.9	nhr-138	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003613	T01B10.4	nhr-14	ges-1, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00018430	F44E7.8	nhr-142	ceh-13, lin-48, ceh-23, dhs-25, mir-243, nhr-178, nhr-86, ref-2, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00015395	C03G6.8	nhr-147	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003615	T12C9.6	nhr-16	nhr-178, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003616	C02B4.2	nhr-17	fat-2, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00017510	F16B4.9	nhr-178	nhr-178	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00018541	F47C10.3	nhr-186	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003601	C32F10.6	nhr-2	peb-1, dhs-25	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003619	F43C1.4	nhr-20	F59F5.2, mir-243, nhr-86, unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00011002	R04B5.3	nhr-205	nhr-178, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003621	K06A1.4	nhr-22	tra-1, nhr-86	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003622	C01H6.5	nhr-23	in vitro binding, egl-46, F53B3.3, inx-6	(Deplancke et al., 2006; PMID 16777607; Kostrouchova et al., 1998; PMID 9521900)
WBGene00012596	Y38E10A.18	nhr-234	ceh-24, nhr-68, nhr-86, T23F11.4	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00021610	Y46H3D.6	nhr-237	nhr-178, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003623	F11C1.6	nhr-25	lin-3, unc-86, vha-15	(Hwang and Sternberg, 2004; PMID 14660442; ; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00022805	ZK697.2	nhr-256	nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00010410	H22D14.1	nhr-267	acs-11, unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00020460	T12C9.1	nhr-273	C15C7.5, cyp-35A3, nhr-178, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003624	C11G6.4	nhr-28	nhr-178, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003602	H01A20.1	nhr-3	ceh-23, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003625	C26B2.3	nhr-31	bioinformatics	(Hahn-Windgassen and Van Gilst, 2009; PMID 19668342)
WBGene00013976	ZK455.6	nhr-33	gpd-3, mir-243, nhr-178, nhr-86, ref-2	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003627	F58G6.5	nhr-34	exp-2, acs-11, ceh-23, nhr-137, nhr-8, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003628	C07A12.3	nhr-35	exp-2, fat-2	(Deplancke et al., 2006; PMID 16777607)
WBGene00018412	F44C4.2	nhr-37	nhr-178	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003603	F32B6.1	nhr-4	exp-2, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00022423	Y104H12A.1	nhr-41	dhs-25	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003632	C33G8.6	nhr-42	mir-243, nhr-178, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003633	C29E6.5	nhr-43	hlh-6, ech-6, lin-4, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003635	F16H11.5	nhr-45	daf-3, nhr-178, nhr-86, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003636	C45E5.6	nhr-46	exp-2	(Deplancke et al., 2006; PMID 16777607)
WBGene00003637	C24G6.4	nhr-47	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003639	K10C3.6	nhr-49	ceh-23, dhs-25, elt-4, nhr-137, nhr-178, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003604	Y73F8A.21	nhr-5	elt-4, gpd-3, lin-4, nhr-137, unc-86, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003643	K06B4.11	nhr-53	nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003605	C48D5.1	nhr-6	in vitro binding, C06E7.3, F59F5.2, far-7, H32C10.3	(Heard et al., 2010; PMID 20506374; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003656	T09A12.4	nhr-66	C18A11.1, cog-1, dac-1, fat-2, nhr-86, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003657	C08F8.8	nhr-67	T05B4.8, nhr-137, nhr-178, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003659	T23H4.2	nhr-69	exp-2, M01D1.2	(Deplancke et al., 2006; PMID 16777607)
WBGene00003660	Y51A2D.17	nhr-70	nhr-178, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003661	K11E4.5	nhr-71	nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003662	C17A2.8	nhr-72	acs-11, C15C7.5, cyp-35A3, dac-1, ech-6, elo-2, elt-4, F55B11.4, F59F5.2, fat-2, mir-243, nhr-137, nhr-86, T23F11.4, unc-86, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003668	F36A4.14	nhr-78	nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003669	T26H2.9	nhr-79	nhr-178, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003607	F33D4.1	nhr-8	pqn-60	(Deplancke et al., 2006; PMID 16777607)
WBGene00003674	T06C12.7	nhr-84	pqn-60, nhr-178	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003676	Y40B10A.8	nhr-86	egg-2, nhr-178, nhr-86, ref-2	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003678	K08A2.5	nhr-88	ceh-23, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003682	Y41D4B.8	nhr-92	cog-1, dac-1, fat-2, nhr-86, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003686	F44C8.11	nhr-96	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003689	M02H5.1	nhr-99	nhr-68	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003779	Y75B8A.2	nob-1	psa-3	(Arata et al., 2006; PMID 16824957)
WBGene00044508	C18F3.4	nsy-7	srsx-3, ceh-23, cog-1	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003845	B0280.4	odd-1	sma-1, tra-1	(Deplancke et al., 2006; PMID 16777607)
WBGene00003854	T18D3.2	odr-7	cdr-4, ceh-24, daf-16, daf-3, emb-5, F26A10.2, ges-1, hlh-6, nhr-68, R06F6.6, T22C8.3, zag-1, cog-1, cyp-35A3, ech-6, egg-2, F55B11.4, F59F5.2, fat-2, gpd-3, lin-4, mir-243, nhr-178, nhr-68, nhr-8, nhr-86, ref-2, str-47, T23F11.4, unc-86, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003909	F45B8.4	pag-3	in vitro binding, T05B4.8, T14G10.4, nhr-178, nhr-8	(Deplancke et al., 2006; PMID 16777607; Zweidler-Mckay et al., 1996; PMID 8754800; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003912	C38D4.6	pal-1	hlh-1, daf-3, elt-4, inx-6, lin-29, lit-1, mab-23, T22H9.4, ceh-23, hlh-15, tag-257	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003937	K07C11.1	pax-1	lit-1	(Deplancke et al., 2006; PMID 16777607)
WBGene00007042	C26C6.1	pbrm-1	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003968	T14F9.4	peb-1	myo-2, dac-1, daf-12, nhr-86	(Beaster-Jones and Okkema, 2004; PMID 15165844; Thatcher et al., 2001; PMID 11203704; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00003976	T28H11.4	pes-1	ChIP	(Niu et al., 2011; PMID 21177963)
WBGene00004013	F38A6.1	pha-4	in vitro binding, ChIP, myo-2, ceh-22, hlh-3, nhr-178, nhr-68, many others	(Gaudet and Mango, 2002; PMID 11823633; Kalb et al., 1998; PMID 9584117; Niu et al., 2011; PMID 21177963; Okkema and Fire, 1994; PMID 7925019; Raharjo et al., 2010; PMID 20623595; Vilimas et al., 2004; PMID 14738885; Zhong et al., 2010; PMID 20174564; Reece-Hoyes et al., 2011; PMID 22037705
WBGene00004024	Y75B8A.1	php-3	ceh-5, R06F6.6, C06E7.3, cog-1, elt-4, F55B11.4, fat-2, hlh-15, nhr-178, nhr-68, tag-257, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00004077	W10C8.2	pop-1	psa-3, ceh-22	(Arata et al., 2006; PMID 16824957; Lam et al., 2006; PMID 16461282)
WBGene00004096	F40F8.7	pqm-1	ChIP, pos-1, tra-1, dac-1, lin-4, mir-243, nhr-86, unc-86, vha-15	(Deplancke et al., 2006; PMID 16777607; Niu et al., 2011; PMID 21177963; ; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00004194	C34C6.6	prx-5	nhr-178	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00019878	R05D3.3	R05D3.3	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00011060	R06C1.6	R06C1.6	daf-3, acs-11, cog-1, dac-1, fat-2, unc-86, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00021538	Y42H9AR.3	rabs-5	T23G5.3	(Deplancke et al., 2006; PMID 16777607)
WBGene00004334	T01E8.2	ref-1	bioinformatics	(De Masi et al., 2011; PMID 21335608)
WBGene00004335	C47C12.3	ref-2	ttx-3, dac-1, nhr-178, unc-86	(Bertrand and Hobert, 2009; PMID 19386265; ; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00004393	B0414.2	rnt-1	rnt-1	(Shim and Lee, 2008; PMID 18158917)
WBGene00017406	F12E12.5	sdz-12	daf-12	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00004764	K04G11.2	sel-7	elt-4	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00004771	C32E12.5	sem-2	mir-77, unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00004773	F15C11.1	sem-4	cog-1, fat-2, vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00004786	F44A6.2	sex-1	dhs-25, lin-4	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00004804	T19E7.2	skn-1	ChIP, microarray, med-1, med-2, end-1, gcs-1, die-1, pop-1	(An and Blackwell, 2003; PMID 12869585; Blackwell et al., 1994; PMID 7939715; Carroll et al., 1997; PMID 9303538; Maduro et al., 2001; PMID 11463373; Niu et al., 2011; PMID 21177963; Oliveira et al., 2009; PMID 19575768; Walker et al., 2000; PMID 10764775
WBGene00013350	Y59A8B.13	slr-2	ceh-24	(Deplancke et al., 2006; PMID 16777607)
WBGene00004857	R13F6.9	sma-3	tra-1	(Deplancke et al., 2006; PMID 16777607)
WBGene00004858	R12B2.1	sma-4	unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00010868	M04G12.4	somi-1	acs-11, dac-1, mdt-15, nhr-86, T23F11.4, unc-86, vha-15, ztf-27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00004949	K08A8.2	sox-2	daf-3, sma-2, unc-86	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00012735	Y40B1A.4	sptf-3	F53B3.3	(Deplancke et al., 2006; PMID 16777607)
WBGene00013111	Y51H4A.17	sta-1	n.d.	(Wang and Levy, 2006; PMID 16873887)
WBGene00044068	ZK867.1	syd-9	daf-12, mir-243	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00011864	T20F10.2	T20F10.2	opt-2	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00020758	T24C4.2	T24C4.2	nhr-68	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006380	F31E8.3	tab-1	cyp-33C8, elt-4, F38B6.1, nhr-22, ztf-4, acs-2, C15C7.5, ceh-23, cyp-35A5, elt-4, far-7, fat-7, his-14, lbp-8, mdt-15, nhr-8, opt-2, ztf-27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006547	F40H6.4	tbx-11	acs-11, ceh-23, cog-1, dac-1, ech-6, egg-2, elo-2, elt-4, F55B11.4, fat-2, mir-243, nhr-178, nhr-8, nhr-86, T23F11.4, unc-86, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006549	Y59E9AR.3	tbx-30	vab-7	(Pocock et al., 2004; PMID 15102704)
WBGene00006552	Y66A7A.8	tbx-33	C15C7.5, dac-1, nhr-178, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006556	Y47D3A.12	tbx-37	egg-2, elo-2	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006557	C24H11.3	tbx-38	T05B4.8, T14G10.4, egg-2, elt-4	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006558	Y73F8A.16	tbx-39	cog-1, fat-2, unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006559	Y73F8A.17	tbx-40	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006545	T07C4.2	tbx-8	ceh-24, dpr-1, ets-4, exp-2, fat-5, T14G10.4, acs-11, acs-2, C06E7.3, C30F12.1, ceh-23, cyp-35A5, daf-12, dhs-25, dop-3, ech-6, egg-2, elo-2, elt-4, F08F8.2, F55B11.4, F59F5.2, far-7, fat-2, fat-4, fat-6, fat-7, gpd-3, hlh-15, lin-4, lpd-2, mdt-15, nhr-137, nhr-178, nhr-68, nhr-8, nhr-86, opt-2, ref-2, str-47, T23F11.4, tag-257, vha-15, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006546	T07C4.6	tbx-9	C06E7.3, C30F12.1, ceh-23, cyp-35A5, daf-12, dhs-25, dop-3, ech-6, egg-2, elo-2, elt-4, F55B11.4, far-7, fat-2, fat-4, fat-6, fat-7, gpd-3, lin-4, lpd-2, mir-243, nhr-137, nhr-178, nhr-8, ref-2, T23F11.4, tag-257, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006580	T23G4.1	tlp-1	daf-3, zag-1	(Deplancke et al., 2006; PMID 16777607)
WBGene00006604	Y47D3A.6	tra-1	xol-1, ceh-30, egl-1, mab-3, rnt-1	(Conradt and Horvitz, 1999; PMID 10458607; Deplancke et al., 2006; PMID 16777607; Hargitai et al., 2009; PMID 19906855; Peden et al., 2007; PMID 18056429; Yi et al., 2000; PMID 11003845; Yi and Zarkower, 1999; PMID 9927589; Zarkower and Hodgkin, 1993; PMI
WBGene00014232	ZK1128.6	ttll-4	F53B3.3	(Deplancke et al., 2006; PMID 16777607)
WBGene00006652	Y113G7A.6	ttx-1	ceh-23, nhr-68, nhr-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006654	C40H5.5	ttx-3	ceh-23 and 38 other AIY terminal genes	(Wenick and Hobert, 2004; PMID 15177025)
WBGene00006853	C47G2.2	unc-130	unc-129, ChIP, F55B11.4, fat-2, nhr-68	(Nash et al., 2000; PMID 11018016; Niu et al., 2011; PMID 21177963; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006743	Y16B4A.1	unc-3	odr-10	(Kim et al., 2005; PMID 16143323)
WBGene00006766	B0564.10	unc-30	unc-25, unc-47, ceh-23	(Eastman et al., 1999; PMID 10414952; Jin et al., 1994; PMID 7997265; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006744	F26C11.2	unc-4	VB motorneuron genes, F55B11.4	(Winnier et al., 1999; PMID 10557206; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006778	F58E6.10	unc-42	acdh-1, acs-11, C15C7.5, ceh-23, cog-1, cyp-35A5, dac-1, ech-6, egg-2, F55B11.4, F59F5.2, far-7, fat-2, hlh-15, lbp-8, mir-243, nhr-68, T23F11.4, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006796	T28F12.2	unc-62	W01C9.1	(Deplancke et al., 2006; PMID 16777607)
WBGene00006818	C30A5.7	unc-86	ceh-30, dac-1	(Peden et al., 2007; PMID 18056429; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006881	R07B1.1	vab-15	acs-11, C15C7.5, ceh-23, cog-1, cyp-35A5, dac-1, ech-6, egg-2, elt-4, F55B11.4, F59F5.2, fat-2, hlh-15, lbp-8, nhr-178, nhr-68, nhr-86, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006870	F14F3.1	vab-3	acs-11, ceh-23, cog-1, cyp-35A5, dac-1, ech-6, elt-4, F55B11.4, F59F5.2, fat-2, lbp-8, mir-243, nhr-137, nhr-178, nhr-68, vha-15, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00001514	C05D2.5	xnd-1	ceh-2, daf-3, K07D4.6, lin-48	(Deplancke et al., 2006; PMID 16777607)
WBGene00012471	Y17G7B.20	Y17G7B.20	nhr-86, Y57A10A.27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00012551	Y37D8A.11	Y37D8A.11	lpd-2	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00021411	Y38C9A.1	Y38C9A.1	egl-46, inx-6, acs-11, C06E7.3, cyp-35A3, ech-6, egg-2, F55B11.4, fat-2, fat-7, his-14, hlh-15, lbp-8, lin-4, lpd-2, mdt-15, mir-243, nhr-178, nhr-68, nhr-8, nhr-86, ref-2, str-47, Y57A10A.27, ztf-27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00013380	Y62E10A.14	Y62E10A.14	ceh-13, W06F12.3	(Deplancke et al., 2006; PMID 16777607)
WBGene00022042	Y65B4BR.5	Y65B4BR.5	exp-2	(Deplancke et al., 2006; PMID 16777607)
WBGene00006970	F28F9.1	zag-1	zag-1, F59F5.2	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00022562	ZC204.12	ZC204.12	C18A11.1, ceh-5, daf-3, die-1, elt-1, F13H10.1, K07D4.6, lin-48, nhr-28, pop-1, pos-1, pqn-60, sma-3, acs-11, C30F12.1, ceh-23, cog-1, cyp-35A3, dac-1, ech-6, egg-2, elo-2, F55B11.4, fat-2, fat-4, lpd-2, nhr-86, T23F11.4, unc-86, vha-15, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00019327	K02F3.4	zip-2	nhr-68, mir-243	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00012330	W07G1.3	zip-3	ZK287.1	(Deplancke et al., 2006; PMID 16777607)
WBGene00021552	Y44E3B.1	zip-4	C18A11.1	(Deplancke et al., 2006; PMID 16777607)
WBGene00011130	R07H5.10	zip-6	dac-1	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00014253	ZK1320.3	ZK1320.3	cog-1	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00018833	F54F2.5	ztf-1	bar-1, C04F12.9, C18A11.1, ceh-13, daf-3, dpr-1, emb-5, end-3, ges-1, inx-6, K07D4.6, lin-48, M01D1.2, mab-23, nhr-28, pos-1, pqn-26, R06F6.6, sma-3, T14G10.4, tra-1, Y38H6C.14, Y49E10.4, zag-1, ztf-4,	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00009939	F52F12.6	ztf-11	M01D1.2, unc-86, vha-15, acs-11, C15C7.5, ceh-23, cog-1, cyp-35A3, dac-1, daf-12, dop-3, ech-6, egg-2, elo-2, F55B11.4, F59F5.2, far-7, fat-2, fat-4, fat-6, gpd-3, H32C10.3, lin-4, mdt-15, mir-243, nhr-137, nhr-68, nhr-8, nhr-86, str-47, T23F11.4, unc-86, vha-15, Y57A10A.27	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00018704	F52E4.8	ztf-13	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00010936	M163.2	ztf-14	vha-15	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00011066	R06C7.9	ztf-15	ceh-23	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00011639	T09A5.12	ztf-17	mir-77	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00020848	T27B1.2	ztf-19	acs-11, cog-1, ech-6, elt-4, fat-2, nhr-68, unc-86	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00008762	F13G3.1	ztf-2	ZK682.5, B0507.1, fat-5, inx-6, M01D1.2, acs-11, egg-2	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00012988	Y48C3A.4	ztf-22	cog-1, fat-2	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00011661	T09F3.1	ztf-27	vha-15, ztf-27	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00016905	C53D5.4	ztf-3	daf-19, gpd-3, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00020399	T10B11.3	ztf-4	rnt-1	(Deplancke et al., 2006; PMID 16777607)
WBGene00012317	W06H12.1	ztf-6	lin-48, T23F11.4, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00009772	F46B6.7	ztf-7	daf-3	(Deplancke et al., 2006; PMID 16777607)
WBGene00022598	ZC395.8	ztf-8	pos-1, ZK682.5, acs-11, C30F12.1, ceh-23, cog-1, dac-1, ech-6, elo-2, far-7, fat-2, fat-4, mdt-15, nhr-86, str-47, vha-15	(Deplancke et al., 2006; PMID 16777607; Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00013966	ZK287.6	ztf-9	dac-1	(Reece-Hoyes et al., 2011; PMID 22037705)
WBGene00006999	F42G4.3	zyx-1	lin-4	(Reece-Hoyes et al., 2011; PMID 22037705)

5.5 Transcription Factor Gene Expression

Transcription factor gene expression is often highly regulated, and understanding the spatial and temporal expression patterns of transcription factors is a key to determining their function. While a variety of transcription factors have been characterized individually using reporter genes, antibodies and in situ hybridizations (e.g., hlh-1, pha-4, ceh-22, tbx-37, unc-86, cnd-1, end-3) (Finney and Ruvkun, 1990; PMID 2257628; Good et al., 2004; PMID 15056620; Hallam et al., 2000; PMID 10976055; Horner et al., 1998; PMID 9649499; Kalb et al., 1998; PMID 9584117; Krause et al., 1990; PMID 2175254; Maduro et al., 2007; PMID 16979152; Okkema and Fire, 1994; PMID 7925019), high throughput techniques such as cell type-specific microarrays and SAGE analyses are providing genome-wide gene expression data (Fox et al., 2005; PMID 15780142; McKay et al., 2003; PMID 15338614; Meissner et al., 2009; PMID 19557190; Roy et al., 2002; PMID 12214599; Spencer et al., 2011; PMID 21177967; Von Stetina et al., 2007; PMID 17612406; Zhang et al., 2002; PMID 12124626). This useful data is available for transcription factor genes (and all other genes) online through WormBase.org and modENCODE.org, while additional analyses regarding tissue specificity are available at http://www.vanderbilt.edu/wormdoc/wormmap/Welcome.html (Spencer et al., 2011; PMID 21177967). In addition, automated analyses of fluorescent protein reporter gene expression are accelerating our knowledge of transcription factor gene expression during embryogenesis and in L1 larvae (Liu et al., 2009; PMID 19879847; Murray et al., 2008; PMID 18587405) (Figure 5). Lineage-based gene expression data generated using these high throughput approaches can be accessed online through EPIC (http://epic.gs.washington.edu/) and WormDB (http://www.computationalbio.com/Stanford/KimLab/wormDB/). This data is useful to investigators interested in specific transcription factors, but it also opens the exciting possibility of using computational approaches to overlay and identify correlations between gene expression patterns to understand how networks of transcription factors control development (Figure 5).

Figure 5. Automated analyses of transcription factor gene expression.

(A–D) Representative frames showing expression of mCherry reporters for the indicated transcription factors (red) ovelayed on ubiquitous histone::gfp reporter expression marking all nuclei. Anterior is left. (E) Embryonic lineage trees showing expression of the indicated transcription factor::mCherry transgenes (colored), or a merged image showing expression of all four transgenes. This data was acquired and visualized using StarryNite and AceTree (Murray et al., 2008; PMID 18587405). Panels A–D were acquired from movies at http://epic.gs.washington.edu/. Panel E was adapted with permission from Murray et al., 2008; PMID 18587405.

5.6 Post-Transcriptional Regulation of Transcription Factor Function

Covalent post-translational modifications also play important roles in regulating transcription factor function (Tootle and Rebay, 2005; PMID 15714552), and a variety of C. elegans transcription factors are regulated by modifications including phosphorylation, proteolysis, ubiquitination, and SUMOylation. For example, nuclear localization and DNA-binding activity of the FoxO-family factor DAF-16 is negatively regulated by the DAF-2/insulin like signaling pathway through phosphorylation at phylogenetically conserved sites (Cahill et al., 2001; PMID 11124266; Lin et al., 2001; PMID 11381260), whereas DAF-16 protein stability is regulated by ubiquitination (Li et al., 2007; PMID 17276341). Likewise the Gli family factor TRA-1 activity is regulated by specific proteolytic cleavage and by ubiquitin mediated targeting to the proteosomal degradation pathway (Schvarzstein and Spence, 2006; PMID 17084364; Starostina et al., 2007; PMID 17609115). Both the ETS-family factor LIN-1 and the T-box factor TBX-2 require SUMOylation (Leight et al., 2005; PMID 15689373; Roy Chowdhuri et al., 2006; PMID 16701625), and at least 20 other transcription factors have been identified as possible SUMOylation targets (Kaminsky et al., 2009; PMID 19922876). SUMOylation of LIN-1 promotes interaction with MEP-1, a component of the NuRD transcriptional repression complex (Leight et al., 2005; PMID 15689373). Transcription factor SUMOylation has also been shown to recruit Drosophila MEP-1 and the NuRD complex, suggesting a conserved mechanism for SUMOylation dependent transcriptional repressors (Stielow et al., 2008; PMID 18374648).

Non-covalent interactions of transcriptional co-activators or co-repressors with DNA-bound transcription factors are also crucial for transcription factor function. The transcriptional co-activator p300/CBP is important for embryonic development (Shi and Mello, 1998; PMID 9531533), while the co-repressors CtBP and SIR-2.1 play important roles regulating life span (Chen et al., 2009; PMID 19164523; Tissenbaum and Guarente, 2001; PMID 11242085). The best-studied transcriptional co-repressor in C. elegans is the Groucho-family factor UNC-37, which was first characterized based on its interaction with the homeodomain factor UNC-4 (Winnier et al., 1999; PMID 10557206). Not surprisingly, UNC-37/Groucho has also been shown to function with a variety of transcription factors in C. elegans, including POP-1, COG-1, REF-1, RNT-1 UNC-30, and MLS-1 (Calvo et al., 2001; PMID 11742996; Chang et al., 2003; PMID 12952888; Miller and Okkema, 2011; PMID 21852953; Neves and Priess, 2005; PMID 15935776; Peden et al., 2007; PMID 18056429; Xia et al., 2007; PMID 17706957). The number of transcription factors that function as UNC-37 dependent repressors is likely to be larger, as potential Groucho-interaction motifs are found in many C. elegans transcription factors (Copley, 2005; PMID 16309560).

6. Chromatin Status and Transcription

The initiation, elongation, and termination of transcription is influenced by both local and chromosome-wide chromatin configuration, and vice versa. Many excellent reviews provide in depth treatments of this topic (Berger, 2010; PMID: 21467136; Yun et al., 2011; PMID: 21423274; and Bannister and Kouzarides, 2011; PMID: 21321607). Here, basic information that is generally applicable across species is briefly summarized prior to a discussion of chromatin regulatory complexes in C. elegans.

Nucleosomes, around which DNA is wound, are composed of a histone protein octamer (two each of H2A, H2B, H3, and H4) that can be post-translationally modified in a variety of ways. Typically, residues on the amino terminal tails of individual histones are modified by phosphorylation, methylation, acetylation, and ubiquitination. The specific amino acid residue of the histone protein that is targeted, the type of modification, and the location of the nucleosome relative to the gene body, can all have effects on transcription, or be altered by transcriptional events. These effects include altering nucleosome density and changing the level of chromatin compaction to either relax or condense a region, which has been predicted to facilitate or prohibit association of different transcriptional regulatory complexes. Additionally, histone modifications can provide specific recruitment sites for different transcriptional regulatory complexes. Moreover, the number of methyl groups modifying a particular residue can have distinct effects on gene expression. As one example, monomethylation of lysine 20 of histone H4 affects transcription, while dimethylation is associated with DNA repair and trimethylation facilitates heterochromatin formation (Balakrishnan and Milavetz, 2010; PMID 20735237). Finally, protein variants of histones, such as H2A.z or CENPA, can be incorporated into the core histone octamer, with differential effects on chromatin configuration and function as well, through regulating noncoding RNA transcription in centromeric regions (reviewed in Stimpson and Sullivan, PMID: 20675111).

Over the past several years, the role of histone modifications, histone variants, and histone modifying enzymes in regulating gene expression during C. elegans development has become clearer. Genome-wide studies of the distribution of individual chromatin marks provide a glimpse into the complex combinatorial “codes” that are possible and that are associated with gene expression (Figure 6). Core chromatin regulatory complexes that have been studied in other organisms, such as NuRD, MLL/COMPASS, and PcG, are also present in recognizable form in C. elegans. An extensive review of germline chromatin is available as a separate chapter in WormBook (see chapter Germline Chromatin), so here we focus on somatic functions of these chromatin regulatory complexes.

Figure 6. Examples of ChIP-chip data for RNA polymerase II (Pol II) and five different histone modifications.

The X axis represents a stretch of Chr IV from nt 12,341,610 to 12,472,625. Coding genes are shown below, with arrows marking the direction of transcription 5'>3'. The Y axis represents the z-score of the log 2 ratios of IP/Input (mean centered and scaled to stdev=1). Note the opposing pattern of H3K27me, a mark associated with gene silencing, with that of activation marks such as H3K4me and H3K36me. Image courtesy of Susan Strome and Andreas Rechsteiner.

6.1 The NuRD Complex

NuRD (Nucleosome Remodeling and Deacetylase) is an evolutionarily conserved complex correlated with transcriptional repression that is required for proper development in mammals (reviewed in (Ho and Crabtree, 2010; PMID 20110991)). The NuRD complex primarily targets lysine 9 of histone H3 for deacetylation, paving the way for a histone methyltransferase (HMT) to methylate the residue. Methylated lysine 9 is then bound by HP1 (heterochromatin protein 1), which induces gene silencing (Brehm et al., 1998; PMID 9468139). In C. elegans, NuRD consists of HDA-1 (histone deacetylase), LIN-53 (RbAp48), LIN-40 (MTA), and one of two Mi2 subunits, either LET-418 (with MEP-1) or CHD-3. The combinatorial nature of NuRD complex components allows both target gene and tissue specificity for repression. In vulval development, both complexes act redundantly (von Zelewsky et al., 2000; PMID 11076750), whereas the complex containing LET-418 and MEP-1 also acts to suppress the germline fate in somatic tissues (Passannante et al., 2010; PMID 21060680; Unhavaithaya et al., 2002; PMID 12507426). The histone methyltransferases that likely methylate the deacetylated lysine 9 residue are MET-1 and/or MET-2 (Andersen and Horvitz, 2007; PMID 17634190).

6.2 The MLL/COMPASS Complex

The MLL/COMPASS (Mixed Lineage Leukemia/Complex Proteins Associated with Set1) complex is responsible for the methylation of lysine 4 of histone H3 (reviewed in (Shilatifard, 2008; PMID 18508253)). In contrast to lysine 9, methylation of lysine 4 is correlated with active gene expression. This complex generally contains seven subunits, all of which are present in C. elegans, including two MLL-like histone methyltransferases (set-2 and set-16), ash-2, rbbp-5, three wdr5-like proteins (wdr-5.1, .2, and .3), cfp-1, and either wdr-82 or dpy-30 (Li and Kelly, 2011; PMID 21455483). Various components have been implicated in dosage compensation (Pferdehirt et al., 2011; PMID 21363964), vulval development (Fisher et al., 2010; PMID 20188723), neuronal development (Poole et al., 2011; PMID: 21698137), and aging (Greer et al., 2010; PMID 20555324). This complex potentially functions antagonistically to NuRD/HP1 in certain aspects, such as growth and somatic gonad development (Simonet et al., 2007; PMID 17967446). Whether NuRD/HP1 and MLL/COMPASS target the same genes or distinct genes in these various developmental processes is currently unknown.

6.3 The Polycomb Group Complex

The Polycomb Group (PcG) of chromatin regulators were first uncovered in the classic studies of Ed Lewis in Drosophila because of their critical roles in maintaining the repressed state of homeotic (Hox) genes regulating segmentation (reviewed in (Muller and Kassis, 2006; PMID 16914306)). Subsequent work by numerous groups over the years reveals that the PcG includes two types of complexes, PRC1 and PRC2. A major role for mammalian PRC2 is repression of Hox gene expression during development by promoting histone H3 lysine 27 methylation, a mark that is then bound by the silencing complex PRC1, which ubiquitylates histone H2A. The mechanism by which this modification leads to Hox gene silencing is not clear. In C. elegans, the PcG-related components were first identified in maternal effect sterile (MES) screens due to their role in the germline (Capowski et al., 1991; PMID 1783292), a topic explored in detail in WormBook chapter Specification of the Germ Line. In the C. elegans soma, at least some PcG-related proteins of the PRC2 complex (MES-2 and MES-6) appear to have a role in regulating Hox gene expression, as is observed in other animals (Deng et al., 2007; PMID 17574230; Ross and Zarkower, 2003; PMID 12791273). Moreover, MES-2 is required for restricting the developmental plasticity of embryos through global changes to the chromatin state (Yuzyuk et al., 2009; PMID 19460346). Until recently, it was less clear whether C. elegans contained a PRC1-like complex. However, certain PRC1-related components are present, including MIG-32/Bmi-1 and SPAT-3/Ring1B, which were shown to be required for H2A ubiquitylation in the soma (Karakuzu et al., 2009; PMID 19211678). Moreover, mig-32 and spat-3 mutants have somatic defects similar to mes-2, suggesting that they act to regulate the same genes. Intriguingly, however, mig-32 and spat-3 do not share the germline defects of mes-2, suggesting that the mechanism of PRC2 activity in the germline is distinct from that of the soma (Karakuzu et al., 2009; PMID 19211678).

6.4 The SynMuv Pathway

Genetic studies in C. elegans have also uncovered a series of intertwined, genetically-linked pathways involving chromatin modifications that affect developmental pathways called the SynMuv pathway (reviewed in (Fay and Yochem, 2007; PMID 17434473)). Consisting of at least three genetically defined groups (A, B, and C), the SynMuv groups reveal the functional redundancy underlying gene regulation (Figure 7). Under standard conditions, genes from at least two of the SynMuv groups must be disrupted by mutation before significant effects in development occur, typically and historically read out as defects in vulva formation in the hermaphrodite. All three groups contain genes that encode gene regulatory proteins, although the SynMuv A group is unique to C. elegans (Davison et al., 2011; PMID 21196525). SynMuv C genes encode proteins of the TipA/HAT regulatory complex that is associated with H3K4 acetylation and active gene expression (Ceol and Horvitz, 2004; PMID 15068795). The best-studied pathway, SynMuv B, includes members of the DRM complex (Harrison et al., 2006; PMID 17075059), which is related to a repressor complex called dREAM in Drosophila (Korenjak et al., 2004; PMID 15479636) and DREAM/Myb-MuvB/LINC in mammals (Knight et al., 2009; PMID 19252525). In C. elegans, DRM includes the sequence-specific binding factor E2F called EFL-1, a pocket protein called LIN-35, and other factors with less well-understood functions, but it does not contain a Myb-like protein as in other organisms (Harrison et al., 2006; PMID 17075059). DRM potentially acts with the deacetylase NuRD complex to promote transcriptional repression, and indeed, microarray studies of mutants in the SynMuv B group primarily show increased abundance of target transcripts (Kirienko and Fay, 2007; PMID 17368442). DRM components are widely expressed, and appear to play diverse roles in many tissues, although in most cases the function of the DRM complex is not solely essential for normal development. However, a second mutation that disrupts a tissue-specific regulatory protein along with a mutation in a DRM complex member can cause a tissue-specific phenotype. For instance, mutation of the C2H2 zinc finger gene slr-2 in conjunction with lin-35 mutations disrupts intestinal function, while either mutation alone does not (Kirienko et al., 2008; PMID 18437219). Additionally, a recent report indicates that one SynMuvB component, LIN-61, which binds methylated lysine 9 of H3 (Koester-Eiserfunke and Fischle, 2011; PMID 21437264), can act as part of the DRM complex in vulval development but not in other processes, showing that this complex has tissue-specificity (Harrison et al., 2007; PMID 17409073). Finally, environmental influences such as temperature can have an effect as well. lin-35, and certain other components of the DRM complex, are required to suppress the germline fate in somatic tissues (Wang et al., 2005; PMID 16049496), but only at higher temperatures is the onset of the germline fate sufficiently severe to lead to a larval arrest (Petrella et al., 2011; PMID 21343362).

Figure 7. Outline of genes in each group of the SynMuv pathway.

SynMuv A and SynMuv B are the major groups in this pathway that are redundantly required for vulval development. The relationship of these pathways with the SynMuv C pathway are less clear. Within the SynMuv B group, LIN-53, marked with an asterisk, is listed twice, as it is found in both NuRD and DRM complexes.

As in other systems, the landscape of chromatin modifications, and the complexes carrying them out, are generally conserved in C. elegans. Thus, it is likely that information from any one experimental system will inform our general understanding of chromatin influences in all systems. In the future, investigating how these different chromatin regulatory complexes interact at common target loci, and how they influence key sequence-specific transcription factors and the core transcriptional machinery, will be critical for understanding gene regulatory mechanisms. The molecular and genetic advantages of C. elegans, combined with a relatively simple and defined cell lineage, suggest that the worm will prove particularly important for understanding the role of chromatin in developmental processes.

7. Systematic Genome-Scale Analysis of Transcription Regulation

Genome-wide analyses complement detailed single-gene studies by providing a global overview that can be used to determine how broadly observations of transcriptional regulatory mechanisms at individual genes are applicable. Over the last decade, microarray analysis of gene expression has been widely used to examine gene expression changes upon perturbation of various transcriptional components. However, one limitation to this type of analysis is the inability to distinguish direct from indirect effects. The more recent development of techniques such as chromatin immunoprecipitation (ChIP), which maps the binding events of a given factor throughout the genome, can overcome this limitation and provide important information about the direct activity of the factor. Chromatin fragments that immunoprecipitate with a chromatin or transcriptional regulatory proteins are identified by either hybridization to a microarray (ChIP-chip) or by deep sequencing (ChIP-seq). This approach has proved to be a very powerful tool for investigating and discovering transcriptional mechanisms. In C. elegans, ChIP studies have been performed by individual labs focused on particular processes or factors, including dosage compensation components (Ercan et al., 2007; PMID 17293863; Jans et al., 2009; PMID 19270160), the DRM complex component LIN-54 (Tabuchi et al., 2011; PMID 21589891), the histone variant HTZ-1 (Whittle et al., 2008; PMID 18787694) and transcription factors such as HLH-1 and NFI-1 (Lei et al., 2010; PMID 21209968; Whittle et al., 2009; PMID 19584245).

7.1 The modENCODE Project

In addition to individual efforts, a large-scale effort by a multi-lab consortium has systematically utilized a genomics approach to exploring C. elegans gene expression. The modENCODE consortium (model organism Encyclopedia of DNA Elements), funded by the National Human Genome Research Institute (NHGRI), has in the last few years produced a wealth of genome-wide C. elegans datasets. These studies explore many aspects of transcriptional regulation, including transcription factor binding sites, chromatin modifications, gene expression analysis of diverse RNAs, including small noncoding RNAs in addition to polyadenylated RNAs (Gerstein et al., 2010; PMID 21177976). A similar effort to analyze the Drosophila melanogaster genome is ongoing as well (Roy et al., 2010; PMID 21177974). The ultimate goal of these projects is to identify, as comprehensively as possible, all of the functional elements encoded in the DNA that are responsible for the regulation and formation of that organism.

A major effort of modENCODE is to determine the binding sites of sequence-specific transcription factors genome-wide. These elements direct the temporal and spatial control of transcription, which in turn dictates an organism’s development, physiology and response to the environment. Identifying these elements provides an important first step toward understanding how DNA sequence is interpreted to form a three-dimensional body plan. At the beginning of the modENCODE project, almost nothing was known about the direct targets of transcription factors in C. elegans. By the time the project completes its fifth year in March 2012, the genome-wide binding profiles of over 120 factors from diverse families of transcriptional regulators will have been collected and released to the C. elegans community.

7.2 modENCODE Transcription Factor ChIP Studies

To systematically identify binding sites, transgenic lines expressing GFP-tagged transcription factors were subjected to ChIP-seq using an antibody to GFP (Zhong et al., 2010; PMID 20174564). The GFP expression patterns of these lines largely recapitulated known endogenous expression patterns, and all lines that were tested robustly rescued the mutant phenotype of that gene, indicating that the tagged transcription factors retain wild type function. All of the detailed protocols and datasets are freely available at www.modencode.org. Moreover, all the strains for which successful datasets have been produced are available in the CGC. So far, 77 completed datasets are available representing 46 transcription factors, some of which have been analyzed at multiple developmental stages (Table 4).

TF proteins	stage(s)	Histone modifications	stage(s)	Chromatin proteins	stage(s)
alr-1	L2	total H3	EE, L3	HPL-2	LE
aly-2	L1, L3	H3K27ac	EE, L3	LIN-15B	LE
ama-1	EE, LE, MxE, L1, starved L1, L2, L3, L4, L4/YA, YA	H3K27me1	EE, L3	pol2	EE, LE
blmp-1	L1	H3K27me3	EE, L3	ama-1	MxE
C01B12.2	L2	H3K36me1	EE, L3	HCP-3	EE, MxE
ceh-14	L2	H3K36me2	EE	CBP	MxE
ceh-26	LE	H3K36me3	EE, LE, L1, L2, L3, L4, YA	HTZ-1	MxE
ceh-30	L3	H3K4me1	EE, L3	DPY-26	MxE
ces-1	L1, L4	H3K4me2	EE, L3	DPY-27	MxE, EE, L4
daf-12	L3, L4	H3K4me3	EE, LE, L1, L2, L3, L4, YA	DPY-28	MxE
daf-16	L4	H3K79me1	MxE, L3	LEM-2	MxE
dpl-1	L1, YA	H3K79me2	EE, MxE, L3	MES-4	EE
dpy-27	MxE	H3K79me3	EE, MxE, L3	MIX-1	MxE
efl-1	L1, YA	H3K9me1	EE, L3	MRG-1	EE
egl-27	L1	H3K9me2	EE, L3
egl-5	L3	H3K9me3	EE, L3
elt-3	L1	total H4	L3
eor-1	L3	H4acTetra	EE
F16B12.6	L1	H4K16ac	EE
F45C12.2	L3	H4K20me1	EE, LE, L3
fos-1	L1, L2	H4K8ac	EE, L3
gei-11	L2, L4
hlh-1	MxE
hlh-8	L3
lin-11	L2
lin-13	MxE
lin-15B	L3, L4
lin-39	L3
mab-5	L3
mdl-1	L1
mef-2	L1
mep-1	MxE
nhr-105	L3
nhr-111	L2
nhr-28	L3, L4
nhr-6	L2
pes-1	L4
pha-4	MxE, LE, L1, starved L1, L2, YA
pqm-1	L3
R02D3.7	L2
sea-2	L3
skn-1	L1
unc-130	L1
unc-62	L1, L2, L3
W03F9.2	L4/YA
zag-1	L1, L2, L3

EE = early embryo, LE= late embryo, MxE= mixed stage embryos, L1–L4 = larval stages 1–4, YA = young adult

This pipeline was first utilized on the FoxA transcription factor PHA-4 that has important roles in both organ development and environmental responses (Zhong et al., 2010; PMID 20174564). Subsequently, an analysis of the major characteristics of 22 transcription factors describes binding site features and correlations for this larger set, including a preliminary regulatory network analysis (Niu et al., 2011; PMID 21177963). Most of these factors bind thousands of sites in the genome, and the majority of these binding sites near coding genes lie within 500 bp of the predicted transcript start site. A significant insight from the properties of these 22 transcription factors was the recognition that the genome contains hundreds of regions that are broadly permissive for non-specific binding by transcription factors (termed high-occupancy target, or "HOT", regions) (Gerstein et al., 2010; PMID 21177976). Recruitment to a HOT region does not require the sequence-specific binding property of the transcription factor, nor is binding correlated with the regulation of nearby genes. How transcription factors are recruited to HOT sites, and the possible role of chromatin or nuclear organization in this process, is unknown. For those interested in using these data to understand gene regulation by a specific transcription factor, HOT sites should be carefully distinguished from other binding sites that are either unique to or primarily bound by the factor of interest, which are more likely to result in direct regulatory events. Another limitation users should realize when interpreting the genome-wide transcription factor binding profiles is that almost all the experiments were performed in whole animals. Any binding profile for a broadly-expressed transcription factor will therefore be an amalgam of binding in multiple tissues. Currently, tissue-specific profiling techniques are being applied to circumvent this problem.

7.3 modENCODE Chromatin Modification ChIP Studies

In addition to sequence-specific transcription factors, a second modENCODE project has focused on collecting genome-wide ChIP-chip datasets for various chromatin-associated factors as well as for histone modifications. Over 20 histone modifications and 14 factors have been analyzed to date. Unlike the transcription factor studies that analyzed transgenic GFP-tagged proteins, these datasets were generated by using antibodies specific to each factor or modification to monitor their endogenous distribution; many of these antibodies are commercially available. This global analysis of chromatin states has yielded various insights, including the persistence of the germline-established chromatin state in the somatic tissues, highlighted by the existence of chromosomal domains enriched for repressive histone modifications that correlate with increased meiotic recombination rates (Gerstein et al., 2010; PMID 21177976). Additionally, the X chromosome exhibits several distinctive features relative to autosomes, including increased monomethylation of H4K20 and H3K27, and increased nucleosome density (Ercan et al., 2011; PMID 21177966; Liu et al., 2011; PMID 21177964). Importantly, when the chromatin modification status was combined with transcription factor data in predictive algorithms for gene regulatory events, the accuracy of the resulting predictions was greatly improved compared to either alone (Gerstein et al., 2010; PMID 21177976).

7.4 modENCODE Transcription Studies

All of these ChIP-based studies are complemented by modENCODE-based analysis of gene expression at many different developmental stages, tissues, and environmental conditions through the use of deep sequencing and tiling microarrays to monitor transcript identity and abundance. As of October 2011, more than 130 experiments have been analyzed and released to the community. These include analysis of both poly-A-selected RNAs as well as small RNAs. Most of these data have been primarily analyzed with the immediate goal of improving gene annotation, and have led to the identification of thousands of novel exons and splicing events, new small RNAs, including many microRNAs, and improved 5' and 3' UTR mapping (Hillier et al., 2009; PMID 19181841; Kato et al., 2009; PMID 19460142; Mangone et al., 2010; PMID 20522740; see also Jan et al., 2011; PMID 21085120). Improved gene models lead to improved assignment of regulatory events to the correct target genes. Moreover, as additional gene expression data is collected and analyzed, more conclusions will be drawn regarding correlations between regulatory factors and changes in gene expression levels across stages, tissues, and conditions.

Countless biological discoveries are embedded in these deep and complex modENCODE datasets. The published global observations and analyses (Gerstein et al., 2010; PMID 21177976) are just the beginning. Investigation of the data by the larger research community, with their specialized expertise in so many aspects of C. elegans biology, is essential to plumb the full possibilities of the data. To facilitate such endeavors by the C. elegans community, all modENCODE data, along with detailed descriptions of growth and collection conditions and protocols, are available at www.modencode.org. The data are available for bulk download for large-scale analyses and comparisons, but the data for individual experiments or individual genes can be examined as well, for those with a particular focus on a single pathway or process. Data of interest can be selected as "tracks" for viewing on a genome browser as well. In the near future, additional changes will be made to the interface to improve selection and analysis of all interested users. Ultimately, all the data on the modENCODE website will be incorporated into Wormbase. Movement of these data to the Cloud to increase accessibility and facilitate downloads is also a likely possibility in the near future.

8. Future Prospects

There is little doubt that the field of transcriptional regulation in C. elegans is in the midst of an information explosion. We are rapidly acquiring information concerning temporal and spatial patterns of gene expression using genome wide expression assays and automated analyses of fluorescent protein reporter expression. At the same time, we are identifying binding sites for transcription factors and chromatin regulatory factors throughout the genome, and recently developed techniques for isolating specific nuclei will enhance our ability for tissue specific chromatin profiling (Deal and Henikoff, 2010; PMID 20627084). Still, we have only begun to explore other areas of transcriptional regulation. How does higher order organization within nuclei affect gene expression (Meister et al., 2010; PMID 20395364; Ikegami et al., 2010; PMID 21176223)? What impact do post-transcriptional and post-translational mechanisms have on transcription factor activity? Overall, it is an exciting time to study transcriptional regulation in C. elegans. Because of the relative simplicity of C. elegans gene promoters, we can reasonably make connections between transcription factors and their target genes. Understanding this information will help decipher how the information in the genome controls every aspect of C. elegans biology.