A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A.
A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A.
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DOI：
10.1083/jcb.200801009
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发表时间：
2009-01-12
期刊：
影响因子：
--
通讯作者：
Lako M
中科院分区：
文献类型：
--
作者：
Zhang X;Neganova I;Przyborski S;Yang C;Cooke M;Atkinson SP;Anyfantis G;Fenyk S;Keith WN;Hoare SF;Hughes O;Strachan T;Stojkovic M;Hinds PW;Armstrong L;Lako M
在这项研究中，我们发现NANOG是一种主转录因子，通过对细胞周期调控成分的转录调控来调控人类胚胎干细胞（hESCs）的s期进入。染色质免疫沉淀结合基于报告者的转染实验表明，在正常生理条件下，NANOG的c端区域与CDK6和CDC25A基因的调控区域结合。hESCs中CDK6和CDC25A表达的降低表明CDK6和CDC25A都参与了s期调控。NANOG过表达对s期调控的影响可以通过单独下调CDK6或CDC25A来减轻。单独过表达CDK6或CDC25A可以挽救NANOG下调对S期进入的影响，这表明CDK6和CDC25A是NANOG在G1到S期转变过程中的下游细胞周期效应物。
In this study, we show that NANOG, a master transcription factor, regulates S-phase entry in human embryonic stem cells (hESCs) via transcriptional regulation of cell cycle regulatory components. Chromatin immunoprecipitation combined with reporter-based transfection assays show that the C-terminal region of NANOG binds to the regulatory regions of CDK6 and CDC25A genes under normal physiological conditions. Decreased CDK6 and CDC25A expression in hESCs suggest that both CDK6 and CDC25A are involved in S-phase regulation. The effects of NANOG overexpression on S-phase regulation are mitigated by the down-regulation of CDK6 or CDC25A alone. Overexpression of CDK6 or CDC25A alone can rescue the impact of NANOG down-regulation on S-phase entry, suggesting that CDK6 and CDC25A are downstream cell cycle effectors of NANOG during the G1 to S transition.
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