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 | |
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 | |
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 | |
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 | |
 m6A RNA Methylation | Deposited by METTL3-METTL14 Recognized by YTHDFs | m6A on 5'UTR signals for ERV mRNA degradation | [77] |