A single amino acid substitution confers enhanced methylation activity   of mammalian Dnmt3b on chromatin DNA

doi:10.1093/nar/gkq456

CORC > 北京大学 > 生命科学学院

	A single amino acid substitution confers enhanced methylation activity of mammalian Dnmt3b on chromatin DNA
	Shen, Li ; Gao, Ge ; Zhang, Ying ; Zhang, He ; Ye, Zhiqiang ; Huang, Shichao ; Huang, Jinyan ; Kang, Jiuhong
刊名	核酸研究
	2010
关键词	DE-NOVO METHYLATION ICF SYNDROME HISTONE H3 CYTOSINE-5 METHYLTRANSFERASES SACCHAROMYCES-CEREVISIAE PROTEIN SEQUENCES EVOLUTION GENES PATTERNS FAMILY
DOI	10.1093/nar/gkq456
英文摘要	Dnmt3a and Dnmt3b are paralogous enzymes responsible for de novo DNA methylation but with distinguished biological functions. In mice, disruption of Dnmt3b but not Dnmt3a causes global DNA hypomethylation, especially in repetitive sequences, which comprise the large majority of methylated DNA in the genome. By measuring DNA methylation activity of Dnmt3a and Dnmt3b homologues from five species, we found that mammalian Dnmt3b possessed significantly higher methylation activity on chromatin DNA than Dnmt3a and non-mammalian Dnmt3b. Sequence comparison and mutagenesis experiments identified a single amino acid substitution (I662N) in mammalian Dnmt3b as being crucial for its high chromatin DNA methylation activity. Further mechanistic studies demonstrated this substitution markedly enhanced the binding of Dnmt3b to nucleosomes and hence increased the chromatin DNA methylation activity. Moreover, this substitution was crucial for Dnmt3b to efficiently methylate repetitive sequences, which increased dramatically in mammalian genomes. Consistent with our observation that Dnmt3b evolved more rapidly than Dnmt3a during the emergence of mammals, these results demonstrated that the I662N substitution in mammalian Dnmt3b conferred enhanced chromatin DNA methylation activity and contributed to functional adaptation in the epigenetic system.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000283116600016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Biochemistry & Molecular Biology; SCI(E); 5; ARTICLE; 18; 6054-6064; 38
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/395533]
专题	生命科学学院
推荐引用方式 GB/T 7714	Shen, Li,Gao, Ge,Zhang, Ying,et al. A single amino acid substitution confers enhanced methylation activity of mammalian Dnmt3b on chromatin DNA[J]. 核酸研究,2010.
APA	Shen, Li.,Gao, Ge.,Zhang, Ying.,Zhang, He.,Ye, Zhiqiang.,...&Kang, Jiuhong.(2010).A single amino acid substitution confers enhanced methylation activity of mammalian Dnmt3b on chromatin DNA.核酸研究.
MLA	Shen, Li,et al."A single amino acid substitution confers enhanced methylation activity of mammalian Dnmt3b on chromatin DNA".核酸研究 (2010).