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Nucleic Acids Research, 2002, Vol. 30, No. 14 3202-3213
© 2002 Oxford University Press

Identification of Sox-2 regulatory region which is under the control of Oct-3/4–Sox-2 complex

Mizuho Tomioka, Masazumi Nishimoto, Satoru Miyagi, Tomoko Katayanagi, Nobutaka Fukui1, Hitoshi Niwa1, Masami Muramatsu and Akihiko Okuda*

Division of Developmental Biology, Saitama Medical School Research Center for Genomic Medicine, 1397-1 Yamane Hidaka-City, Saitama 350-1241, Japan and 1 Laboratory for Pluripotent Cell Studies, RIKEN, Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan

*To whom correspondence should be addressed. Tel: +81 429 85 7267; Fax: +81 429 85 7264; Email: akiokuda{at}saitama-med.ac.jp
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors

Sox-2 is a transcriptional cofactor expressed in embryonic stem (ES) cells as well as in neuronal cells. It has been demonstrated that Sox-2 plays an important role in supporting gene expression in ES cells, especially by forming a complex with embryonic Octamer factor, Oct-3/4. Here, we have analyzed the regulatory regions of the Sox-2 gene and identified two enhancers which stimulate transcription in ES cells as well as in embryonal carcinoma cells. These regulatory regions, which we termed Sox regulatory regions (SRR) 1 and 2, exert their function specifically when cells are in an undifferentiated state. Interestingly, like the regulatory elements of FGF-4 and UTF1 genes, combinatorial action of Octamer and Sox-2 binding sites support the SRR2 activity. However, biochemical analyses reveal that, due to the unique sequence and/or its organization, the SRR2 bears distinct characteristics from those of FGF-4 and UTF1 regulatory elements. That is, unlike the FGF-4 gene enhancer, the SRR2 precludes the binding of the Oct-1–Sox-2 complex. The difference between the SRR2 and UTF1 regulatory element is in the ability of SRR2 to recruit the Oct-6–Sox-2 complex as well as the Oct-3/4–Sox-2 complex. Co-transfection analyses confirm that both complexes are able to stimulate transcription through the SRR2 element.


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