This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Sun, C.
Right arrow Articles by Yokota, T.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, C.
Right arrow Articles by Yokota, T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2009, p. 4574-4583, Vol. 29, No. 16
0270-7306/09/$08.00+0     doi:10.1128/MCB.01863-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Dax1 Binds to Oct3/4 and Inhibits Its Transcriptional Activity in Embryonic Stem Cells{triangledown} ,{dagger}

Chuanhai Sun,1,{ddagger} Yuhki Nakatake,2,4,{ddagger} Tadayuki Akagi,1,{ddagger} Hiroki Ura,1,{ddagger} Takahiko Matsuda,3 Akira Nishiyama,4 Hiroshi Koide,1 Minoru S. H. Ko,4 Hitoshi Niwa,2* and Takashi Yokota1*

Department of Stem Cell Biology, Graduate School of Medical Science, Kanazawa University, Ishikawa 920-8640, Japan,1 Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan,2 Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts,3 Developmental Genomics & Aging Section, Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland 212244

Received 5 December 2008/ Returned for modification 28 January 2009/ Accepted 28 May 2009

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.

* Corresponding author. Mailing address for Hitoshi Niwa: Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chu-o-ku, Kobe 650-0047, Japan. Phone: 81-78-306-1927. Fax: 81-78-306-1929. E-mail: niwa{at}cdb.riken.jp. Mailing address for Takashi Yokota: Department of Stem Cell Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan. Phone: 81-76-265-2205. Fax: 81-76-234-4238. E-mail: tyokota{at}med.kanazawa-u.ac.jp

{triangledown} Published ahead of print on 15 June 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors contributed equally to this work.

Molecular and Cellular Biology, August 2009, p. 4574-4583, Vol. 29, No. 16
0270-7306/09/$08.00+0     doi:10.1128/MCB.01863-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»