期刊
JOURNAL OF CELL BIOLOGY
卷 184, 期 1, 页码 67-82出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200801009
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资金
- Medical Research Council [G0301182]
- Biotechnology and Biological Sciences Research Council [BBS/B/14779]
- One North East Regional Development Agency
- Sir James Knott Trust
- Life Knowledge Park
- Biotechnology and Biological Sciences Research Council [BB/E012841/1, BBS/B/14779] Funding Source: researchfish
- Medical Research Council [G0301182] Funding Source: researchfish
- BBSRC [BB/E012841/1] Funding Source: UKRI
- MRC [G0301182] Funding Source: UKRI
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 immuno-precipitation 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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