論文 - 詳細
RRC ID | 28455 |
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著者 | Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R, Sharov AA, Ko MS, Niwa H. |
タイトル | Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. |
ジャーナル | 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. |
巻・号 | 9(6) |
ページ | 625-35 |
公開日 | 2007-6-1 |
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 | 20.042 |
引用数 | 753 |
WOS 分野 | CELL BIOLOGY |
リソース情報 | |
遺伝子材料 | pSRR2 tk-luc (RDB07095) pNanog-luc (RDB12116) pBRCMhCMV*1-Sox2-IZ (RDB12121) pBRPyCAG-tTAFF-IN (RDB12109). |