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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Greer Card, D. A.
Right arrow Articles by Archer, T. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Greer Card, D. A.
Right arrow Articles by Archer, T. K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2008, p. 6426-6438, Vol. 28, No. 20
0270-7306/08/$08.00+0     doi:10.1128/MCB.00359-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Oct4/Sox2-Regulated miR-302 Targets Cyclin D1 in Human Embryonic Stem Cells{triangledown} ,{dagger}

Deborah A. Greer Card,1,{ddagger} Pratibha B. Hebbar,1,{ddagger} Leping Li,2 Kevin W. Trotter,1 Yoshihiro Komatsu,3 Yuji Mishina,3 and Trevor K. Archer1*

Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis,1 Biostatistics Branch,2 Molecular Developmental Biology Group, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 277093

Received 3 March 2008/ Returned for modification 21 April 2008/ Accepted 8 August 2008

Oct4 and Sox2 are transcription factors required for pluripotency during early embryogenesis and for the maintenance of embryonic stem cell (ESC) identity. Functional mechanisms contributing to pluripotency are expected to be associated with genes transcriptionally activated by these factors. Here, we show that Oct4 and Sox2 bind to a conserved promoter region of miR-302, a cluster of eight microRNAs expressed specifically in ESCs and pluripotent cells. The expression of miR-302a is dependent on Oct4/Sox2 in human ESCs (hESCs), and miR-302a is expressed at the same developmental stages and in the same tissues as Oct4 during embryogenesis. miR-302a is predicted to target many cell cycle regulators, and the expression of miR-302a in primary and transformed cell lines promotes an increase in S-phase and a decrease in G1-phase cells, reminiscent of an ESC-like cell cycle profile. Correspondingly, the inhibition of miR-302 causes hESCs to accumulate in G1 phase. Moreover, we show that miR-302a represses the productive translation of an important G1 regulator, cyclin D1, in hESCs. The transcriptional activation of miR-302 and the translational repression of its targets, such as cyclin D1, may provide a link between Oct4/Sox2 and cell cycle regulation in pluripotent cells.

* Corresponding author. Mailing address: Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, 111 Alexander Drive, MD D4-01, P.O. Box 12233, Research Triangle Park, NC 27709. Phone: (919) 316-4565. Fax: (919) 316-4566. E-mail: archer1{at}niehs.nih.gov

{triangledown} Published ahead of print on 18 August 2008.

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

{ddagger} These authors contributed equally to this study.

Molecular and Cellular Biology, October 2008, p. 6426-6438, Vol. 28, No. 20
0270-7306/08/$08.00+0     doi:10.1128/MCB.00359-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wang, Y., Blelloch, R. (2009). Cell Cycle Regulation by MicroRNAs in Embryonic Stem Cells. Cancer Res. 69: 4093-4096 [Abstract] [Full Text]  
  • Freemantle, S. J., Guo, Y., Dmitrovsky, E. (2009). Retinoid Chemoprevention Trials: Cyclin D1 in the Crosshairs. Cancer Prevention Research 2: 3-6 [Full Text]  


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