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The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells

来自 Nature

阅读量：

413

作者：

YH Loh，Q Wu，JL Chew，VB Vega，W Zhang，X Chen，G Bourque，J George，B Leong，J Liu

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摘要：

Oct4 and Nanog are transcription factors required to maintain the pluripotency and self-renewal of embryonic stem (ES) cells. Using the chromatin immunoprecipitation paired-end ditags method, we mapped the binding sites of these factors in the mouse ES cell genome. We identified 1,083 and 3,006 high-confidence binding sites for Oct4 and Nanog, respectively. Comparative location analyses indicated that Oct4 and Nanog overlap substantially in their targets, and they are bound to genes in different configurations. Using de novo motif discovery algorithms, we defined the cis-acting elements mediating their respective binding to genomic sites. By integrating RNA interference-mediated depletion of Oct4 and Nanog with microarray expression profiling, we demonstrated that these factors can activate or suppress transcription. We further showed that common core downstream targets are important to keep ES cells from differentiating. The emerging picture is one in which Oct4 and Nanog control a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination.

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关键词：

Animals Humans Mice DNA-Binding Proteins Homeodomain Proteins Transcription, Genetic Gene Expression Regulation RNA Interference Embryo, Mammalian Octamer Transcription Factor-3

DOI：

10.1038/ng1760

被引量：

5252

年份：

2006

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来源期刊

Nature Genetics

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2009
被引量：572

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