Journal
NATURE CELL BIOLOGY
Volume 10, Issue 2, Pages 194-U68Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb1680
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Funding
- Medical Research Council [G0300723B] Funding Source: researchfish
- Wellcome Trust Funding Source: Medline
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Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Self-renewal of mouse ES cells depends on activation of Stat3 by leukaemia inhibitory factor (LIF) in collaboration with bone morphogenetic protein signalling(1-3). The transcription factor Nanog is essential in maintaining pluripotency(4,5) but the mechanisms involved are poorly understood. Here we examine the functional interactions of Nanog with the Stat3 and NF kappa B pathways. Nanog and Stat3 were found to bind to and synergistically activate Stat3-dependent promoters. We also found that Nanog binds to NF kappa B proteins; however, Nanog binding inhibited transcriptional activity of NF kappa B proteins. Endogenous NF kappa B activity and target-gene expression increased during differentiation of ES cells. Overexpression of NF kappa B proteins promoted differentiation, whereas inhibition of NF kappa B signalling, either by genetic ablation of the Ikbkg gene or overexpression of the I kappa B alpha super-repressor, increased expression of pluripotency markers. We conclude that Nanog represses the pro-differentiation activities of NF kappa B and cooperates with Stat3 to maintain pluripotency.
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