3svm | pdb_00003svm
Human MPP8 - human DNMT3AK47me2 peptide
Structural highlights
Function[MPP8_HUMAN] Involved in transcriptional regulation. Specifically recognizes and binds methylated 'Lys-9' of histone H3 (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.[1] [DNM3A_HUMAN] Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZNF238. Can actively repress transcription through the recruitment of HDAC activity (By similarity).[2] Publication Abstract from PubMedDNA CpG methylation and histone H3 lysine 9 (H3K9) methylation are two major repressive epigenetic modifications, and these methylations are positively correlated with one another in chromatin. Here we show that G9a or G9a-like protein (GLP) dimethylate the amino-terminal lysine 44 (K44) of mouse Dnmt3a (equivalent to K47 of human DNMT3A) in vitro and in cells overexpressing G9a or GLP. The chromodomain of MPP8 recognizes the dimethylated Dnmt3aK44me2. MPP8 also interacts with self-methylated GLP in a methylation-dependent manner. The MPP8 chromodomain forms a dimer in solution and in crystals, suggesting that a dimeric MPP8 molecule could bridge the methylated Dnmt3a and GLP, resulting in a silencing complex of Dnmt3a-MPP8-GLP/G9a on chromatin templates. Together, these findings provide a molecular explanation, at least in part, for the co-occurrence of DNA methylation and H3K9 methylation in chromatin. MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a.,Chang Y, Sun L, Kokura K, Horton JR, Fukuda M, Espejo A, Izumi V, Koomen JM, Bedford MT, Zhang X, Shinkai Y, Fang J, Cheng X Nat Commun. 2011 Nov 15;2:533. doi: 10.1038/ncomms1549. PMID:22086334[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||||||
