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 | Â | Â | Â | Â | |
H4 (5,12) | Histone deposition | HAT1 | Â | Â | Â | Â | |
H4 (5,8,12,16), H3(14) | Activation, DNA repair | TIP60 | Â | Â | Â | Â | |
H4 (5,8,12) | Â | HB01 | Â | Â | Â | Â | |
 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 | Â | Â | Â | Â | |
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 | Â | Â | Â | Â | |
H4 (20) | Repression, activation, DNA repair, cell cycle | Pr-SET(7,8), SUV4 20H(1,2) | Â | Â | Â | Â | |
 Eraser | H3 (4) | Downregulation of proximal genes | LSD1, BHC110, jumonji class | Human endogenous enhancer | TALE | LSD1 FL | [32] |
H3 (36) | Â | JHDM 1 (a, b), JMJD2A/JHDM3A, JMJD2C/GASC1 | Â | Â | Â | Â | |
H3 (9) | Â | JHDM 2 (a, b), JMJD2 (B, D), JMJD2A/ JHDM3A, JMJD2C/GASC1, LSD1 | Â | Â | Â | Â | |
Arginine (Rme) | |||||||
 Writer | H3 (2, 17, 26) | Activation | CARM1 |  |  |  |  |
H4 (3) | Activation | PRMT4 | Â | Â | Â | Â | |
Ubiquitylation | |||||||
 Lysine (Kub) | |||||||
 Writer | H2B (123/120) | Activation | RNF (20, 40) |  |  |  |  |
H2A (119) | Repression | Bmi/Ring1A | Â | Â | Â | Â | |
Phosphorylation | |||||||
 Threonine (Tph) | |||||||
 Writer | H3 (3) | Mitosis |  |  |  |  |  |
 Serine (Sph) | |||||||
 Writer | H3 (28) | Immediate-early activation | MSK (1,2) |  |  |  |  |
H4 (1) | Mitosis | Â | Â | Â | Â | Â | |
H2A (139) | DNA repair | ATR, ATM, DNA-PK | Â | Â | Â | Â | |
H2B (14) | Apoptosis | Mst1 | Â | Â | Â | Â | |
Proline isomerization | |||||||
 Proline (Pisom) | |||||||
 Writer | H3 (30, 38) | Activation/repression | ScFPR4 |  |  |  |  |