Pluripotency Governed by Sox2 Via Regulation of Oct3/4 Expression in Mouse Embryonic Stem Cells.
From: Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Minatojima-minamimachi 2-2-3, Chu-o-ku, Kobe, Hyogo 650-0047, Japan. masui@ri.imcj.go.jp
Nature cell biology
- Publish Date: Jun 2007
- ISSN: 1465-7392
- Volume: 9
- Issue: 6
- Pages: 625-35
- Medium: Print
- Language: English
- Citation (JAMA): Masui Shinji, Nakatake Yuhki, Toyooka Yayoi, et al. Pluripotency Governed by Sox2 Via Regulation of Oct3/4 Expression in Mouse Embryonic Stem Cells.. Nat. Cell Biol. Jun 2007;9:625-35
Abstract
The pluripotency of embryonic stem (ES) cells is thought to be maintained by a few key transcription factors, including Oct3/4 and Sox2. The function of Oct3/4 in ES cells has been extensively characterized, but that of Sox2 has yet to be determined. Sox2 can act synergistically with Oct3/4 in vitro to activate Oct-Sox enhancers, which regulate the expression of pluripotent stem cell-specific genes, including Nanog, Oct3/4 and Sox2 itself. These findings suggest that Sox2 is required by ES cells for its Oct-Sox enhancer activity. Using inducible Sox2-null mouse ES cells, we show that Sox2 is dispensable for the activation of these Oct-Sox enhancers. In contrast, we demonstrate that Sox2 is necessary for regulating multiple transcription factors that affect Oct3/4 expression and that the forced expression of Oct3/4 rescues the pluripotency of Sox2-null ES cells. These results indicate that the essential function of Sox2 is to stabilize ES cells in a pluripotent state by maintaining the requisite level of Oct3/4 expression.
Mesh Headings (Keywords): Animals, Cell Differentiation, Cell Line, Cells, Cultured, DNA-Binding Proteins, Embryonic Development, Embryonic Stem Cells, Enhancer Elements (Genetics), Gene Expression Regulation, Developmental, Homeodomain Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Octamer Transcription Factor-3, Organic Cation Transport Proteins, Pluripotent Stem Cells, Trans-Activation (Genetics), Trans-Activators, Transcription Factors, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 17515932
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