Cdk2ap1 Is Required for Epigenetic Silencing of Oct4 during Murine Embryonic Stem Cell Differentiation

被引：33

作者：

Deshpande, Amit M. ^{[1
]}

Dai, Yan-Shan ^{[1
]}

Kim, Yong ^{[1
]}

Kim, Jeffrey ^{[1
]}

Kimlin, Lauren ^{[1
]}

Gao, Kai ^{[1
]}

Wong, David T. ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Sch Dent, Dent Res Inst, Los Angeles, CA 90025 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 10期

基金：

美国国家卫生研究院;

关键词：

LEUKEMIA INHIBITORY FACTOR; TUMOR-SUPPRESSOR GENE; SELF-RENEWAL; DNA METHYLATION; MOUSE EMBRYO; PLURIPOTENCY; EXPRESSION; NURD; COMPONENT; NETWORK;

D O I：

10.1074/jbc.C800158200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Oct4 is a known master regulator of stem cell renewal and differentiation. Expression of Oct4 during differentiation is regulated by promoter methylation by the nucleosome remodeling and histone deacetylation (NuRD) complex. Here, we show that Cdk2ap1, a negative regulator of Cdk2 function and cell cycle, promotes Oct4 promoter methylation during murine embryonic stem cell differentiation to down-regulate Oct4 expression. We further show that this repressor function of Cdk2ap1 is dependent on its physical interaction with the methyl DNA-binding protein, Mbd3. Our data support a potential molecular link between the known differentiation promoters, including bone morphogenetic proteins and transforming growth factor signaling, and embryonic stem cell differentiation.

引用

页码：6043 / 6047

页数：5

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