title: MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a.
abstract: 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.
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Yanqi
authors.initials: Y
authors.lastname: Chang
authors.forename: Lidong
authors.initials: L
authors.lastname: Sun
authors.forename: Kenji
authors.initials: K
authors.lastname: Kokura
authors.forename: John R
authors.initials: JR
authors.lastname: Horton
authors.forename: Mikiko
authors.initials: M
authors.lastname: Fukuda
authors.forename: Alexsandra
authors.initials: A
authors.lastname: Espejo
authors.forename: Victoria
authors.initials: V
authors.lastname: Izumi
authors.forename: John M
authors.initials: JM
authors.lastname: Koomen
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bedford
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shinkai
authors.forename: Jia
authors.initials: J
authors.lastname: Fang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
mesh_terms: D002151:Calorimetry; D002460:Cell Line; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D000090205:DNA Methyltransferase 3A; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse; D006649:Histocompatibility Antigens; C547278:MPHOSPH8 protein, human; D010750:Phosphoproteins; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C445405:EHMT2 protein, human; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase
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