Table 1.
Proteins in the maintenance of DNA methylation imprints (adapted from [15]).
| Protein | Description | Methylation Phenotype due to Loss of Expression, or Knock-Down, in Somatic Cells or Embryos | References |
|---|---|---|---|
| DNA Methyltransferases (DNMTs) and Other DNA Methylation-Related Proteins: | |||
| DNMT1 | maintenance DNA methyltransferase | Loss of imprinting control region (ICR) DNA methylation. | [32] |
| DNMT3A DNMT3B | de novo DNA methyltransferases |
Dnmt3a−/− embryonic stem cells (ES) cells: ICR hypomethylation Double-Knock out (KO)embryos: partial loss of ICR methylation at Rasgrf1 and Peg3. |
[32,34] |
| UHRF1 (NP95) |
binds hemi-methylated DNA post-replication and recruits DNMT1 | Loss of ICR methylation. | [35] |
| MBD3 | methyl CpG-binding domain protein-3 | Loss of ICR methylation at Igf2-H19 locus. | [36] |
| ZFP57 | Krüppel associated box (KRAB) domain zinc finger protein | Reduced methylation at human ICRs (PLAGL1, GRB10, and PEG3 loci). | [37,38] |
| ZFP445 | KRAB domain zinc finger protein | Human embryonic stem cells (ESCs): loss of ICR methylation at MEG3 and IGF2-H19 loci. Zfp445−/− Zfp57−/− double KO embryos: loss of methylation at almost all ICRs. |
[39] |
| KAISO (ZBTB33) |
Zinc Finger and Broad-complex, Tramtrack and Bric- à brac (BTB) Domain Containing-33 | Loss of ICR methylation at the human IGF2-H19 imprinted locus. | [40] |
| Histones and Other Chromatin-Related Proteins: | |||
| Histones H1 | linker histones | Triple knockout (H1c,d,e): reduced ICR methylation at Igf2-H19 and Dlk1-Dio3. | [41] |
| SETDB1 | H3 lysine-9-specific histone methyl-transferase | Loss of H3K9me3 at ICRs, loss of DNA methylation at Meg3, Nespas, Mest, Peg3. | [42,43] |
| DPPA3 (PGC7, Stella) |
methylated histone (H3K9me2) binding protein | Partial loss of DNA methylation at several ICRs. | [44,45] |
| KAP1 (TRIM28) |
KRAB-associated protein 1 | Partial loss of methylation at several ICRs (Igf2-H19 and Snrpn loci). | [46] |
| ATRX | H3.3 histone chaperone | Loss of histone variant H3.3 and H3K9me3 at ICRs; no reported effects on DNA methylation. | [47] |
| Other Proteins: | |||
| NAA10P (ARID1) |
N-alfa-acetyltransferase 10 | Loss of ICR/DMR methylation at Trappc9-Peg13, Kcnq1-Kcnq1ot1, Mest, Snrpn, Grb10 and H19. | [48] |
| NLRP2 | cytoplasmic caterpillar family protein | Loss of methylation at ICR of KCNQ1 domain. | [49] |
| NLRP5 | cytoplasmic caterpillar family protein | Decrease in methylation PLAGL1, IGF2R, GRB10, MEST, KCNQ1OT1, MEG3 and PEG3. | [50] |
| MTA2 | Metastasis tumor antigen-2 | Partial losses of ICR methylation at Igf2-H19 and Peg3 domains. | [51] |
| RBBP1 and RBBP1L1 | Retinoblastoma (Rb)-binding proteins | Combined knockout: loss of ICR methylation at the Prader-Willi syndrome (PWS) (Snrpn) imprinted gene domain. | [52] |
| SMCHD1 | Hinge domain protein | ICR hypo-methylation at Peg12 and Snrpn. | [53] |