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Molecular and Cellular Biology, May 2004, p. 4207-4220, Vol. 24, No. 10
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.10.4207-4220.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Sox-2 Regulatory Regions Display Their Activities in Two Distinct Types of Multipotent Stem Cells

Satoru Miyagi,1,2 Tetsuichiro Saito,3 Ken-ichi Mizutani,3 Norihisa Masuyama,4 Yukiko Gotoh,4 Atsushi Iwama,5 Hiromitsu Nakauchi,5 Shinji Masui,6 Hitoshi Niwa,6 Masazumi Nishimoto,1 Masami Muramatsu,1 and Akihiko Okuda1*

Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical School, Saitama 350-1241,1 REDS Group, Saitama Small Enterprise Promotion Corporation, Skip City, Kawaguchi, Saitama 333-0844,2 Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507,3 Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032,4 Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639,5 Laboratory for Cell Pluripotency Studies, RIKEN, Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan6

Received 4 November 2003/ Returned for modification 8 January 2004/ Accepted 18 February 2004

The Sox-2 gene is expressed in embryonic stem (ES) cells and neural stem cells. Two transcription enhancer regions, Sox-2 regulatory region 1 (SRR1) and SRR2, were described previously based on their activities in ES cells. Here, we demonstrate that these regulatory regions also exert their activities in neural stem cells. Moreover, our data reveal that, as in ES cells, both SRR1 and SRR2 show their activities rather specifically in multipotent neural stem or progenitor cells but cease to function in differentiated cells, such as postmitotic neurons. Systematic deletion and mutation analyses showed that the same or at least overlapping DNA elements of SRR2 are involved in its activity in both ES and neural stem or progenitor cells. Thus, SRR2 is the first example of an enhancer in which a single regulatory core sequence is involved in multipotent-state-specific expression in two different stem cells, i.e., ES and neural stem cells.


* Corresponding author. Mailing address: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical School, 1397-1 Yamane Hidaka, Saitama 350-1241, Japan. Phone: 81-429-85-7268. Fax: 81-429-85-7264. E-mail: akiokuda{at}saitama-med.ac.jp.


Molecular and Cellular Biology, May 2004, p. 4207-4220, Vol. 24, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.10.4207-4220.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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