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A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A

Lookup NU author(s): Dr Irina Neganova, Dr Stuart Atkinson, Dr George Anyfantis, Dr Owen Hughes, Professor Tom Strachan, Professor Miodrag Stojkovic, Professor Lyle Armstrong, Professor Majlinda LakoORCiD

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Abstract

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.

Publication metadata

Author(s): Zhang X, Neganova I, Przyborski S, Yang CB, Cooke M, Atkinson SP, Anyfantis G, Fenyk S, Keith WN, Hoare SF, Hughes O, Strachan T, Stojkovic M, Hinds PW, Armstrong L, Lako M

Publication type: Article

Publication status: Published

Journal: Journal of Cell Biology

Year: 2009

Volume: 184

Issue: 1

Pages: 67-82

Date deposited: 09/09/2010

ISSN (print): 0021-9525

ISSN (electronic): 1540-8140

Publisher: Rockefeller University Press

URL: http://dx.doi.org/10.1083/jcb.200801009

DOI: 10.1083/jcb.200801009

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