ORIGINAL ARTICLE Cell Research (2009): 1-10 Cross-regulation of the Nanog and Cdx2 promotersLingyi Chen1,2,3,4,5, Akiko Yabuuchi1,2,3,4,5, Sarah Eminli6, Ayumu Takeuchi1,2,3,4,5, Chi-Wei Lu1,2,3,4,5, Konrad Hochedlinger6 and George Q Daley1,2,3,4,5 1Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, MA, USA2Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA 3Division of Hematology, Brigham and Women's Hospital, Boston, MA, USA 4Harvard Stem Cell Institute, Boston, MA, USA 5Howard Hughes Medical Institute, Boston, MA, USA 6Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, Boston, MA, USA
The first cell fate choice in the mammalian embryo, the segregation of the inner cell mass (ICM) and trophectoderm (TE), is regulated by the mutually antagonistic effects of the transcription factors, Oct4 and Cdx2, while the pluripotency factor, Nanog, is essential to specify the epiblast. We have analyzed the promoters of Nanog and Cdx2, and have found that these two transcription factors are likewise regulated reciprocally. Using an embryonic stem cell line with conditional TE differentiation, we show that Nanog overexpression suppresses the upregulation of TE markers, while Nanog knockdown upregulates the expression of TE markers. We further show that Nanog and Cdx2 bind to and repress each other's promoters. However, whereas Nanog knockout results in detectable Cdx2 expression in the ICM, we observe no overt disruption of blastocyst development, indicating that Nanog plays a subservient role to Oct4 in segregation of the ICM and TE. Cell Research advance online publication 30 June 2009; doi: 10.1038/cr.2009.79 Keywords: Cdx2, Nanog, embryonic stem cells, trophectoderm stem cells |
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