MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a

Journal Article · Wed Nov 30 04:00:00 EST 2011 · Nature Communications

DOI:https://doi.org/10.1038/ncomms1549· OSTI ID:1030437

Chang, Yanqi; Sun, Lidong; Kokura, Kenji; Horton, John R; Fukuda, Mikiko; Espejo, Alexsandra; Izumi, Victoria; Koomen, John M; Bedford, Mark T; Zhang, Xing; Shinkai, Yoichi; Fang, Jia; Cheng, Xiaodong ^[1]

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1. Moffitt

DNA 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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE Office of Science (SC)
• OSTI ID: 1030437
• Journal Information: Nature Communications, Journal Name: Nature Communications Journal Issue: (533) ; 11, 2011 Vol. 2
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
CHROMATIN
DIMERS
DNA
GENETICS
HISTONES
IN VITRO
LYSINE
METHYLATION
MODIFICATIONS
PROTEINS