Synergistic function of DNA methyltransferases Dnmt3a and Dnmt3b in the methylation of Oct4 and Nanog

Jing Yu Li, Min Tie Pu, Ryutaro Hirasawa, Bin Zhong Li, Yan Nv Huang, Rong Zeng, Nai He Jing, Taiping Chen, En Li, Hiroyuki Sasaki, Guo Liang Xu

研究成果: ジャーナルへの寄稿学術誌査読

200 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)8748-8759
ページ数12
ジャーナルMolecular and cellular biology
27
24
DOI
出版ステータス出版済み - 12月 2007
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

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