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

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...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of cell biology 2009-01, Vol.184 (1), p.67-82
Main Authors: Zhang, Xin, Neganova, Irina, Przyborski, Stefan, Yang, Chunbo, Cooke, Michael, Atkinson, Stuart P, Anyfantis, George, Fenyk, Stefan, Keith, W. Nicol, Hoare, Stacey F, Hughes, Owen, Strachan, Tom, Stojkovic, Miodrag, Hinds, Philip W, Armstrong, Lyle, Lako, Majlinda
Format: Article
Language:English
Subjects:
Antibodies
Binding sites
Biochemistry
cdc25 Phosphatases - metabolism
Cell cycle
Cell lines
Cell Proliferation
Chromatin
Cyclin-Dependent Kinase 6 - metabolism
Cytometry
Down regulation
Embryology
Embryonic stem cells
Embryonic Stem Cells - cytology
Embryos
G1 Phase
Gene Expression Regulation, Developmental
Genes
Homeodomain Proteins - chemistry
Homeodomain Proteins - metabolism
Homeodomain Proteins - physiology
Humans
Interphase
Nanog Homeobox Protein
Pluripotent Stem Cells - cytology
Regulatory Sequences, Nucleic Acid
S Phase
Signal Transduction
Small interfering RNA
Stem cells
Transcription, Genetic
Transfection
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200801009