Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells

Chuanhai Sun, Yuhki Nakatake, Tadayuki Akagi, Hiroki Ura, Takahiko Matsuda, Akira Nishiyama, Hiroshi Koide, Minoru S.H. Ko, Hitoshi Niwa, Takashi Yokota

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Abstract

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Transcription factor Oct3/4 is an indispensable factor in the self-renewal of ES cells. In this study, we searched for a protein that would interact with Oct3/4 in ES cells and identified an orphan nuclear hormone receptor, Dax1. The association of Dax1 with Oct3/4 was mediated through the POU-specific domain of Oct3/4. Ectopic expression of Dax1 inhibited Oct3/4-mediated activation of an artificial Oct3/4-responsive promoter. Expression of Dax1 in ES cells also reduced the activities of Nanog and Rex1 promoters, while knockdown of Dax1 increased these activities. Pulldown and gel shift assays revealed that the interaction of Dax1 with Oct3/4 abolished the DNA binding activity of Oct3/4. Chromatin immunoprecipitation assay results showed that Dax1 inhibited Oct3/4 binding to the promoter/enhancer regions of Oct3/4 and Nanog. Furthermore, overexpression of Dax1 resulted in ES cell differentiation. Taken together, these data suggest that Dax1, a novel molecule interacting with Oct3/4, functions as a negative regulator of Oct3/4 in ES cells.

Original languageEnglish
Pages (from-to)4574-4583
Number of pages10
JournalMolecular and cellular biology
Volume29
Issue number16
DOIs
Publication statusPublished - 2009 Aug 1

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Sun, C., Nakatake, Y., Akagi, T., Ura, H., Matsuda, T., Nishiyama, A., Koide, H., Ko, M. S. H., Niwa, H., & Yokota, T. (2009). Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells. Molecular and cellular biology, 29(16), 4574-4583. https://doi.org/10.1128/MCB.01863-08