MPHOSPH8 Antibody - #DF9637

Heterochromatin component that specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes recruitment of proteins that mediate epigenetic repression. 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. Binds H3K9me and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene. Mediates down-regulation of CDH1 expression. 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. 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.

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

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

Homodimer. Interacts (via chromo domain) with histone H3K9me3. Has the highest affinity for H3K9me3, and lesser affinity for H3K9me2 and H3K9me1. Component of the HUSH complex; at least composed of TASOR, PPHLN1 and MPHOSPH8. Interacts with DNMT3, EHMT1 and SETDB1. Interacts with MORC2; the interaction associateS MORC2 with the HUSH complex which recruits MORC2 to heterochromatic loci. Interacts with ZNF638; leading to recruitment of the HUSH complex to unintegrated retroviral DNA.

The chromo domain mediates interaction with methylated 'Lys-9' of histone H3 (H3K9me), with the highest affinity for the trimethylated form (H3K9me3).