Reference - Detail
|Author||Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R, Sharov AA, Ko MS, Niwa H.|
|Title||Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells.|
|Journal||Nat. Cell Biol.|
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||Animals Cell Differentiation / physiology* Cell Line Cells, Cultured DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Embryonic Development / physiology Embryonic Stem Cells / metabolism* Enhancer Elements, Genetic / genetics Gene Expression Regulation, Developmental / genetics Homeodomain Proteins / genetics Homeodomain Proteins / metabolism Mice Mice, Inbred C57BL Mice, Knockout Nanog Homeobox Protein Octamer Transcription Factor-3 / genetics Octamer Transcription Factor-3 / metabolism* Organic Cation Transport Proteins / genetics Organic Cation Transport Proteins / metabolism* Pluripotent Stem Cells / metabolism* SOXB1 Transcription Factors Trans-Activators / genetics Trans-Activators / metabolism* Transcription Factors / genetics Transcriptional Activation / genetics Up-Regulation / genetics|
|WOS Category||CELL BIOLOGY|
|DNA material||pSRR2 tk-luc (RDB07095) pNanog-luc (RDB12116) pBRCMhCMV*1-Sox2-IZ (RDB12121) pBRPyCAG-tTAFF-IN (RDB12109).|