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J. Biol. Chem., Vol. 282, Issue 17, 12822-12830, April 27, 2007

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Oct4 and Sox2 Directly Regulate Expression of Another Pluripotency Transcription Factor, Zfp206, in Embryonic Stem Cells^*

Zheng-Xu Wang, Christina Hui-Leng Teh, Jacqueline L. L. Kueh, Thomas Lufkin^¶, Paul Robson^¶, and Lawrence W. Stanton^¶1

From the Department of Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Department of General Surgery, Jin Cheng Hospital of Lan Zhou, Gansu Province 730050, China, and ^¶Department of Biological Sciences, National University of Singapore, Singapore 117543

It is well known that Oct4 and Sox2 play an important role in the maintenance of embryonic stem cell pluripotency. These transcription factors bind to regulatory regions within hundreds of target genes to control their expression. Zfp206 is a recently characterized transcription factor that has a role in maintaining stem cell pluripotency. We have demonstrated here that Zfp206 is a direct downstream target of Oct4 and Sox2. Two composite sox-oct binding sites have been identified within the first intron of Zfp206. We have demonstrated binding of Oct4 and Sox2 to this region. In addition, we have shown that Oct4 or Sox2 alone can activate transcription via one of these sox-oct elements, although the presence of both Oct4 and Sox2 gave rise to a synergistic effect. These studies extend our understanding of the transcriptional network that operates to regulate the differentiation potential of embryonic stem cells.

Received for publication, December 26, 2006 , and in revised form, February 12, 2007.

^* This work was supported by funding from the Singapore government through the Biomedical Research Council and the Agency for Science, Technology, and Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1–3.

¹ To whom correspondence should be addressed: Genome Institute of Singapore, 60 Biopolis St., Singapore 138672. Tel.: 65-6478-8000; Fax: 65-6478-9051; E-mail: stantonl{at}gis.a-star.edu.sg.

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