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Table 1 Molecular writers and erasers of chromatin modifications

From: The epigenome: the next substrate for engineering

Modification Substrate specificity Putative functions Example proteins/domains Epigenetic engineering applications
Target locus DBD CR fusion Reference
DNA
Methylation
 Writer Cytosine Repression DNMT1, DNMT3 Human endogenous promoter ZF hDnmt3a CD [25]
Reporter plasmid in mammalian cells Gal4, ZF mDnmt3a CD, mDnmt3b CD [26]
Mutated mitochondrial DNA ZF hDNMT3a CD [27]
 Eraser Cytosine Activation TET1, TET2, TDG Human endogenous promoter ZF TET1 CD, TET2 CD [28]
Human endogenous promoter TALE, ZF TET1 FL, CD [29]
Mouse endogenous promoter RHD TDG FL [30]
Mouse endogenous promoter ZF TDG FL [31]
Histones
Acetylation
 Lysine (Kac)
 Writer H3 (14,18,27), H4 (5,8), H2A (5), H2B (12,15) Activation CBP/p300 Human endogenous promoter CRISPR/Cas9, ZF, TALE p300 FL, CD [53]
Reporter plasmid in mammalian cells Gal4 p300 FL, CD [131]
Integrated reporter in mammalian cells LexA p300 HAT [132]
H3 (9,14,18) Activation, DNA repair PCAF, GCN5     
H4 (5,12) Histone deposition HAT1     
H4 (5,8,12,16), H3(14) Activation, DNA repair TIP60     
H4 (5,8,12)   HB01     
 Eraser H3 (9, 56), H4 (8, 16) Repressive chromatin establishment, metabolism SIRT1, SIRT2, SIRT3, SIRT5, SIRT6 Integrated reporter in human cells Gal4 SIRT1 FL [133]
Methylation
 Lysine (Kme)
 Writer H3 (4) Activation MLL (1,2,3,4,5), SET1 (A,B), ASH1 Reporter gene in flies Gal4 Ash1 FL, CD [134]
H3 (36) Repression, transcriptional elongation SET2, NSD1, SYMD2 Integrated reporter in yeast LexA Set2 FL, CD [135]
H3 (79) Transcriptional elongation, euchromatin DOT1     
H3 (9) Repression, imprinting SUV39H (1,2), G9a, RIZ1, ESET/SETDB1, EuHMTase/GLP, CLL8, SETDB1 Human endogenous promoter ZF G9a CD, SUV39h1 FL, CD [54]
Integrated reporter in mammalian cells Gal4 G9a FL [136]
Reporter plasmid in mammalian cells Gal4 SUV39h1 FL, CD [137]
H3 (27) Repression EZH1/2, WHSC1     
H4 (20) Repression, activation, DNA repair, cell cycle Pr-SET(7,8), SUV4 20H(1,2)     
 Eraser H3 (4) Downregulation of proximal genes LSD1, BHC110, jumonji class Human endogenous enhancer TALE LSD1 FL [32]
H3 (36)   JHDM 1 (a, b), JMJD2A/JHDM3A, JMJD2C/GASC1     
H3 (9)   JHDM 2 (a, b), JMJD2 (B, D), JMJD2A/ JHDM3A, JMJD2C/GASC1, LSD1     
Arginine (Rme)
 Writer H3 (2, 17, 26) Activation CARM1     
H4 (3) Activation PRMT4     
Ubiquitylation
 Lysine (Kub)
 Writer H2B (123/120) Activation RNF (20, 40)     
H2A (119) Repression Bmi/Ring1A     
Phosphorylation
 Threonine (Tph)
 Writer H3 (3) Mitosis      
 Serine (Sph)
 Writer H3 (28) Immediate-early activation MSK (1,2)     
H4 (1) Mitosis      
H2A (139) DNA repair ATR, ATM, DNA-PK     
H2B (14) Apoptosis Mst1     
Proline isomerization
 Proline (Pisom)
 Writer H3 (30, 38) Activation/repression ScFPR4     
  1. Activation, transcriptional activation; repression, transcriptional repression. See also [34] for examples of engineered histone deacetylases (HDACs), methyltransferases (HMTs), acetyltransferase (HAT) inhibitors, and HDAC- and HMT-recruiting proteins. Other useful references and guides [3, 4, 138, 139]. Abbreviations: TALE transcription activator-like effector, ZF zinc finger