RRC ID 28455
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.
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.
Volume 9(6)
Pages 625-35
Published 2007-6
DOI 10.1038/ncb1589
PII ncb1589
PMID 17515932
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
IF 17.728
Times Cited 587
WOS Category CELL BIOLOGY
Resource
DNA material pSRR2 tk-luc (RDB07095) pNanog-luc (RDB12116) pBRCMhCMV*1-Sox2-IZ (RDB12121) pBRPyCAG-tTAFF-IN (RDB12109).