| Function |
Heterochromatin component that specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes recruitment of proteins that mediate epigenetic repression (PubMed:26022416, PubMed:28581500, PubMed:29211708). As part of the HUSH complex, promotes epigenetic repression of mobile genetic elements, such as retroviruses and transposable elements: the HUSH complex mainly represses LINE-1 (L1) retrotransposons that are still capable of transposition (PubMed:29211708). Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708). MPHOSPH8 mediates recruitment of the HUSH complex to H3K9me3 sites: the HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3, as well as MORC2, a chromatin remodeler that compacts chromatin (PubMed:26022416, PubMed:28581500). The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). As part of the HUSH2 complex, promotes epigenetic repression of interferon-stimulated genes (PubMed:33144593, PubMed:39013473). Binds H3K9me and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene (PubMed:20871592). Mediates silencing of E-cadherin (CDH1) and protocadherin genes in the nervous system (PubMed:20871592). |
4.0
MPHOSPH8
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binding