MPHOSPH8

MPHOSPH8 (M-Phase Phosphoprotein 8) is a Protein Coding gene. Gene Ontology (GO) annotations related to this gene include methylated histone binding.

Full Name

M-PHASE PHOSPHOPROTEIN 8

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:20871592, PubMed:26022416).

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 (PubMed:26022416, PubMed:28581500).

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 down-regulation of CDH1 expression (PubMed:20871592).

Also represses L1 retrotransposons in collaboration with MORC2 and, probably, SETDB1, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708).

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).

Biological Process

Negative regulation of gene expression, epigenetic Source: UniProtKB
Negative regulation of single stranded viral RNA replication via double stranded DNA intermediate Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of DNA methylation-dependent heterochromatin assembly Source: UniProtKB
Regulation of DNA methylation Source: UniProtKB

Cellular Location

Nucleus
Other locations
Chromosome
Note: Detected on heterochromatin (PubMed:20871592, PubMed:26022416). Dissociates from chromatin during interphase and early mitosis (PubMed:23416073). Detected on nucleosomes (PubMed:20871592).

PTM

Phosphorylated in M (mitotic) phase. Phosphorylation by CDK1 promotes dissociation from chromatin.