Synergistic function of DNA Methyltransferases dnmt3a and dnrnt3b in the methylation of Oct4 and Nanog

	Synergistic function of DNA Methyltransferases dnmt3a and dnrnt3b in the methylation of Oct4 and Nanog
	Li, JY; Pu, MT; Hirasawa, R; Li, BZ; Huang, YN; Zeng, R; Jing, NH; Chen, T; Li, E; Sasaki, H
刊名	MOLECULAR AND CELLULAR BIOLOGY
	2007
卷号	27 期号:24 页码:8748-8759
通讯作者	Xu, GL (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Room 300,Bldg Cell Biol,320 Yueyang Rd, Shanghai 200031, Peoples R China.,glxu@sibs.ac.cn
英文摘要	DNA methylation plays an important role in gene silencing in mammals. Two de novo methyltransferases, Dnmt3a and Dnmt3b, are required for the establishment of genomic methylation patterns in development. However, little is known about their coordinate function in the silencing of genes critical for embryonic development and how their activity is regulated. Here we show that Dnmt3a and Dnmt3b are the major components of a native complex purified from embryonic stem cells. The two enzymes directly interact and mutually stimulate each other both in vitro and in vivo. The stimulatory effect is independent of the catalytic activity of the enzyme. In differentiating embryonic carcinoma or embryonic stem cells and mouse postimplantation embryos, they function synergistically to methylate the promoters of the Oct4 and Nanog genes. Inadequate methylation caused by ablating Dnmt3a and Dnmt3b is associated with dysregulated expression of Oct4 and Nanog during the differentiation of pluripotent cells and mouse embryonic development. These results suggest that Dnmt3a and Dnmt3b form a complex through direct contact in living cells and cooperate in the methylation of the promoters of Oct4 and Nanog during cell differentiation. The physical and functional interaction between Dnmt3a and Dnmt3b represents a novel regulatory mechanism to ensure the proper establishment of genomic methylation patterns for gene silencing in development.
学科主题	Biochemistry & Molecular Biology; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]	DE-NOVO METHYLATION ; EMBRYONIC STEM-CELLS ; MAMMALIAN DEVELOPMENT ; CYTOSINE-5 METHYLTRANSFERASES ; ICF SYNDROME ; EXPRESSION ; GENE ; ESTABLISHMENT ; MAINTENANCE ; PATTERNS
收录类别	SCI
语种	英语
WOS记录号	WOS:000251527300028
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1631]
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	Li, JY,Pu, MT,Hirasawa, R,et al. Synergistic function of DNA Methyltransferases dnmt3a and dnrnt3b in the methylation of Oct4 and Nanog[J]. MOLECULAR AND CELLULAR BIOLOGY,2007,27(24):8748-8759.
APA	Li, JY.,Pu, MT.,Hirasawa, R.,Li, BZ.,Huang, YN.,...&Xu, GL.(2007).Synergistic function of DNA Methyltransferases dnmt3a and dnrnt3b in the methylation of Oct4 and Nanog.MOLECULAR AND CELLULAR BIOLOGY,27(24),8748-8759.
MLA	Li, JY,et al."Synergistic function of DNA Methyltransferases dnmt3a and dnrnt3b in the methylation of Oct4 and Nanog".MOLECULAR AND CELLULAR BIOLOGY 27.24(2007):8748-8759.