Table 1. Chromatin marks.
Chromatin mark | “Writers” | “Reader” domains & proteins | “Erasers” | Genomic distribution | Main function as epigenetic mark | Other features |
---|---|---|---|---|---|---|
DNA: | ||||||
5mC | DNA methyltransferases (Dnmts 1, 3a, 3b) |
Methyl-CpG Binding Domains (MBDs) (e.g. MeCP2, MBDs1-4) BTB/POZ domains (Kaiso, ZBTB4, ZBTB38) |
Active demethylation (TET 1,2,3 proteins) Passive demethylation processes |
CpG dinucleotides throughout the genome: intergenic regions, gene bodies, heterochromatin, satellite repeats. Excluded from CpG islands associated with promoters |
Repressive mark Cellular memory |
Essential for chromosome stability, silencing of transposons, genomic imprinting and X-inactivation |
5hmC, 5fC, 5caC | Ten-eleven translocation enzymes (TET 1, 2, 3) |
Unknown | TDG followed by base excision repair (BER) Passive processes |
Oxidation products of 5mC; abundant levels of 5hmC in brain and ES cells | Unknown | Demethylation intermediates of 5mC; Mutations targeting TET genes frequently observed in human cancers |
Histone tails: | ||||||
H3K27me | Histone lysine methyltransferases - HMTs (EZH2) | Chromo and WD40 domains (e.g. Polycomb protein Pc, EED, CBX7) | Histone lysine demethylases- HDMs (KDM6a, KDM6b) |
Repressive domains and silent developmental genes | Repressive mark Cellular memory |
Established by polycomb complex activity; mark associated with bivalent chromatin* |
H3K4me | Lysine HMT (e.g.SETD1a,b,SETD7, NSD3, MLL, PRDM9) |
Chromo, PHD, Tudor, MBT, Zf-W domains (e.g. CHD1, ING2) | HDMs (e.g.KDM1A,5A,5D, PHF8) |
H3K4me1: enhancers H3K4me2: promoters & enhancers H3K4me3: promoters & transcription start sites |
Activating mark | H3K4me3 mark is enriched at CpG islands devoided of DNA methylation & associated with bivalent chromatin* |
H3K9me | Lysine HMT (e.g. G9a/KTM1C, PRDM2, SETDB1-2; SUV39H1-H2/KTM1A-B) | Chromo, PHD, Tudor, WD40 domains, Ankyrin repeats (e.g. HP1, CDY, EED) | HDMs (e.g. KDM1A, 1B, 3A, 3B, 4A, 4C, 4D) |
H3K9me2: heterochromatin H3K9me3: constitutive heterochromatin and repetitive elements |
Repressive mark | The chromodomain of all HP1 isoforms binds to H3K9me3 and this interaction is important for the recruitment of HP1 proteins to heterochromatic areas of the genome. |
H3K36me3 | Lysine HMT (SETD2, NSD2) |
Chromo, PWWP Domains (e.g. EAF3, MRG15, N-PAC) |
HDMs (KDM4A, NO66) |
Associated with transcribed portions of genes, with preference for 3’regions after intron1 | Elongation mark associated with transcription | H3K36me3 regulates DNA mismatch repair (MMR) in human cells, being required to recruit MMR recognition proteins onto chromatin |
H3K4ac | Histone acetyltransferases – HATs (KAT2A/GCN5) |
Bromo Domains | Histone deacetylases-HDAC’s (HDAC3) | Enriched at transcription start sites (TSS) and along gene bodies | Activating mark (“Open” chromatin) |
|
H3K9ac | HATs (e.g. KAT2A/GCN5, ELP3) | Bromo Domains (e.g. BRG1, BRD4, TAF1) |
HDAC’s (SIRT1, SIRT6) | Preference for promoters (near TSS is related to transcriptional activation) |
Activating mark (“Open” chromatin) |
Mark of active regulatory elements |
H3K27ac | HATs (P300, CREBBP/CBP) |
Bromo Domains (e.g. BRG1, BRD4, TAF1) |
HDACs (e.g. HDAC1) |
Active regulatory elements (may distinguish between active promoters and enhancers from inactive ones) | Activating mark (“Open” chromatin) |
Distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone |
contains both activating and repressing marks in the same domain of chromatin; these bivalent domains are considered to “poise” expression of developmental genes, allowing timely activation while maintaining repression in the absence of differentiation signals; for extended information on the chromatin marks listed see review articles: Huang H et al. (2004) Snapshot: Histone modifications Cell, 159:p458; Li E and Zhang Y (2014) DNA methylation in mammals. CSH Perspect Biol 6:a019133; Yun M et al. (2015) Readers of histone modifications. Cell Research 21:564-578; see also main text for details)