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.