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

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

Research output: Contribution to journalArticle

55 Citations (Scopus)

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
Externally publishedYes

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Embryonic Stem Cells
Blastocyst Inner Cell Mass
Orphan Nuclear Receptors
Chromatin Immunoprecipitation
Cytoplasmic and Nuclear Receptors
Genetic Promoter Regions
Cell Differentiation
Transcription Factors
Gels
DNA
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells. / Sun, Chuanhai; Nakatake, Yuki; Akagi, Tadayuki; Ura, Hiroki; Matsuda, Takahiko; Nishiyama, Akira; Koide, Hiroshi; Ko, Minoru; Niwa, Hitoshi; Yokota, Takashi.

In: Molecular and Cellular Biology, Vol. 29, No. 16, 08.2009, p. 4574-4583.

Research output: Contribution to journalArticle

Sun, C, Nakatake, Y, Akagi, T, Ura, H, Matsuda, T, Nishiyama, A, Koide, H, Ko, M, Niwa, H & Yokota, T 2009, 'Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells', Molecular and Cellular Biology, vol. 29, no. 16, pp. 4574-4583. https://doi.org/10.1128/MCB.01863-08
Sun, Chuanhai ; Nakatake, Yuki ; Akagi, Tadayuki ; Ura, Hiroki ; Matsuda, Takahiko ; Nishiyama, Akira ; Koide, Hiroshi ; Ko, Minoru ; Niwa, Hitoshi ; Yokota, Takashi. / Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells. In: Molecular and Cellular Biology. 2009 ; Vol. 29, No. 16. pp. 4574-4583.
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