G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis

被引：496

作者：

Feldman, N

Gerson, A

Fang, J

Li, E

Zhang, Y

Shinkai, Y

Cedar, H

Bergman, Y ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Sch Med, Dept Expt Med, IL-91120 Jerusalem, Israel

[2] Hebrew Univ Jerusalem, Sch Med, Dept Cellular Biochem, IL-91120 Jerusalem, Israel

[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA

[4] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

[5] Kyoto Univ, Inst Virus Res, Expt Res Ctr Infect Dis, Sakyo Ku, Kyoto 6068507, Japan

来源：

NATURE CELL BIOLOGY | 2006年 / 8卷 / 02期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/ncb1353

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Oct-3/4 is a POU domain homeobox gene that is expressed during gametogenesis and in early embryonic cells(1,2), where it has been shown to be important for maintaining pluripotency(3). Following implantation, this gene undergoes a novel multi-step programme of inactivation. Transcriptional repression is followed by a pronounced increase in histone H3 methylation on Lys 9 that is mediated by the SET-containing protein, G9a. This step sets the stage for local heterochromatinization via the binding of HP1 and is required for subsequent de novo methylation at the promoter by the enzymes Dnmt3a/3b. Genetic studies show that these epigenetic changes actually have an important role in the inhibition of Oct-3/4 reexpression, thereby preventing reprogramming.

引用

页码：188 / U55

页数：10

共 33 条

[21] DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development [J].