TABLE 2.

Transcription factor-binding site enrichment analysis

Binding site enrichment analysis was performed on gene sets preferentially regulated by each MEF2 factor using the Genomatix software suite. Fifteen motifs were uniquely enriched in the MEF2A-sensitive gene set, two were enriched in the MEF2B set, no motifs were enriched in the MEF2C set, and two were enriched in the MEF2D set. The table provides the description of each enriched motif with a calculated Z score (Z > 2 was considered significantly enriched). The known binding factors and their relevant binding domains are included. Finally, a summary of the function of each of these binding factors is provided.

TF module	Module description	Z score	Known factor	Binding domain	Function
Mef2a
V$SF1F	Vertebrate steroidogenic factor	13.53	Nr5a1	C4 zinc finger domain	Essential for embryonic sex determination
V$DLXF	Distal-less homeodomain transcription factors	12.93	Dlx1–Dlx6	Homeodomain	Repressor, important of embryonic development (shared function)
V$IKZF	Ikaros family zinc finger 5	10.16	Ikzf5	C2H2 zinc finger domain	Repressor, lymphocyte development
V$BARB	Barbiturate-inducible element box	9.68	Not characterized	Not characterized
V$ZF05	C2H2 zinc finger transcription factor 5	9.49	Zfp410	C2H2 zinc finger domain	ECM remodeling
V$IKRS	Ikaros zinc finger family	8.8	Ikzf1–Ikzf4	C2H2 zinc finger domain	Repressor, lymphocyte development (shared function)
V$THAP	THAP domain containing protein	6.72	Thap1	THAP domain	Cell cycle progression downstream of Rb-E2F signaling
V$HEAT	Heat shock factors	6.34	Hsf1, Hsf2, Hsf4	HSF-HTH	Heat-sensitive activator, embryonic development
V$ATBF	AT-binding transcription factor	6.15	Zfhx3	C2H2 zinc finger domain, C2HC zinc finger domain, homeodomain	Repressor, promotes neuronal and myogenic differentiation
V$OVOL	OVO homolog-like transcription factor	6.15	Ovol1, Ovol2	C2H2 zinc finger domain	Ovol1: repressor, contributes to epithelial development
					Ovol2: repressor, embryonic cardiovascular development
V$GTBX	GT box	4.38	Zfp628	C2H2 zinc finger domain	Uncharacterized transcriptional regulator
V$PTF1	Pancreas transcription factor 1, heterotrimeric transcription factor	4.33	Ptf1a, Rbpj, Rbpjl	Basic helix-loop-helix	Ptf1a: involved in pancreatic and neuronal development
					Rbpj: involved in cardiac and hematopoeitic development
					Rbpjl: uncharacterized transcriptional regulator
V$RU49	Zinc finger transcription factor RU49, zinc finger proliferation 1-Zipro1	3.4	Zscan21	C2H2 zinc finger domain	Uncharacterized transcriptional regulator
V$HZIP	Homeodomain-leucine zipper transcription factors	2.21	Homez	Homeodomain	Uncharacterized transcriptional regulator
V$CHOP	C/EBP homologous protein (CHOP)	2.12	Ddit3	bZIP	Stress sensitive transcriptional regulator, negative regulator of myogenic differentiation
Mef2b
V$BTBF	BTB/POZ (broad complex, TramTrack, Bric-a-brac/pox viruses and zinc fingers)	2.56	Zbtb33	BTB-POZ C2H2 zinc fingers	Repressor of Wnt target genes; activator of an unrelated set of genes
Mef2c
Mef2d
V$TALE	TALE homeodomain class recognizing TG motifs	3.94	Meis1, Meis2, Meis3, Pknox1, Pknox2, Tgif1, Tgif2	TALE class homeodomain	Meis1: angiogenic and hematopoeitic development
					Meis2: mammalian eye/neuronal development
					Meis3: activator, downstream of PKB signaling
					Pknox1: activator, hematopoeitic and angiogenic development
					Pknox2: associated with actin cytoskeleton
					Tgif1: Downstream of TGF-β signaling, embryonic development
					Tgif2: uncharacterized regulator downstream of TGF-β signaling
V$DICE	Downstream immunoglobulin	2.31	Gtf2i, Gtf2ird1	GTF2I repeat domain	Gtf2i: embryonic development, negative regulator of angiogenesis
	Control element, critical for B cell activity and specificity				Gtf2ird1: modulates cell cycle progression, skeletal muscle differentiation