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

	A single amino acid substitution confers enhanced methylation activity of mammalian Dnmt3b on chromatin DNA
	Shen, L; Gao, G; Zhang, Y; Zhang, H; Ye, ZQ; Huang, SC; Huang, JY; Kang, JH
刊名	NUCLEIC ACIDS RESEARCH
	2010
卷号	38 期号:18 页码:6054-6064
通讯作者	Kang, JH (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China.,gaog@mail.cbi.pku.edu.cn ; jhkang@sibs.ac.cn
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.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	DE-NOVO METHYLATION ; ICF SYNDROME ; HISTONE H3 ; CYTOSINE-5 METHYLTRANSFERASES ; SACCHAROMYCES-CEREVISIAE ; PROTEIN SEQUENCES ; EVOLUTION ; GENES ; PATTERNS ; FAMILY
收录类别	SCI
语种	英语
WOS记录号	WOS:000283116600016
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1084]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Shen, L,Gao, G,Zhang, Y,et al. A single amino acid substitution confers enhanced methylation activity of mammalian Dnmt3b on chromatin DNA[J]. NUCLEIC ACIDS RESEARCH,2010,38(18):6054-6064.
APA	Shen, L.,Gao, G.,Zhang, Y.,Zhang, H.,Ye, ZQ.,...&Kang, JH.(2010).A single amino acid substitution confers enhanced methylation activity of mammalian Dnmt3b on chromatin DNA.NUCLEIC ACIDS RESEARCH,38(18),6054-6064.
MLA	Shen, L,et al."A single amino acid substitution confers enhanced methylation activity of mammalian Dnmt3b on chromatin DNA".NUCLEIC ACIDS RESEARCH 38.18(2010):6054-6064.