Table 2.
Known Regulators of hERVs
| Pre-transcriptional | Notable Proteins involved | Function | Sources |
|---|---|---|---|
| ZFPs & TRIM28-SETDB1 |
Recruits HIRA complex, heterodimeric protein complex of DAXX, and ATRX |
Binds to and methylates proximal DNA and trimethylates proximal H3K9 residues to silence the transcription of ZFP-bound ERV loci Replace canonical H3 proteins with the transcriptionally repressive non-canonical H3.3 variant |
[132] [133] |
| HUSH Complex |
Composed of three protein subunits, MPP8, PPHLN1, and TASOR Recruits MORC2 |
Universally represses TE transposition and expression by performing targeted repression of loci corresponding to intron-less RNA | [134–137] |
| SWI-SNF Complex | Composed of PBRM1 | Rearrange location of histone proteins in chromatin, which impacts loci accessibility for epigenetic modification | [138] |
| MORC | Facilitates HUSH, DNA methylators, and DAXX-ATRX | Compacts chromatin through multimeric assemblies that trap DNA loops to restrict access, which influences gene expression | [139] |
| LSH | Facilitates DNMT enzymes and H3K9 trimethylating enzymes | Permits accessibility of DNA transcription factors and chromatin-modifying enzymes to regulate ERV expression | [140, 141] |
| PIWI-interacting RNAs |
Utilizes argonaute proteins Guides H3K9 tri-methylating and DNA methylating enzymes |
Guides DNA and histone silencing activity proximal to loci complementary to the piRNA guide | [142] |
| Post-transcriptional | |||
| PIWI-interacting RNAs | Utilizes argonaute proteins | Recognize and cleave complementary ERV mRNAs | [142] |
| NEXT Complex |
Composed of RBM7, ZCCHC8, and MTR4 Recruited by HUSH |
Degrades intron-less RNA | [143, 144] |
| m6A RNA Methylation |
Deposited by METTL3-METTL14 Recognized by YTHDFs |
m6A on 5'UTR signals for ERV mRNA degradation | [77] |
HIRA histone regulator A, DAXX death-domain-associated protein, ATRX ATP-dependent helicase, MPP8 methyl-H3K9-binding protein PPHLN1 periphilin 1, TASOR transcription activation suppressor, MORC2 microrchidia 2, PBRM1 Polybromo 1, DNMT DNA methyltransferase, RBM7 RNA-binding motif protein 7, ZCCHC8 zinc-finger CCHC-type containing 8, MTR4 ATP-dependent RNA helicase DOB1