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.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / physiology*
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Cell Line
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Cells, Cultured
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Embryonic Development / physiology
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Embryonic Stem Cells / metabolism*
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Enhancer Elements, Genetic / genetics
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Gene Expression Regulation, Developmental / genetics
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nanog Homeobox Protein
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Octamer Transcription Factor-3 / genetics
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Octamer Transcription Factor-3 / metabolism*
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Organic Cation Transport Proteins / genetics
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Organic Cation Transport Proteins / metabolism*
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Pluripotent Stem Cells / metabolism*
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SOXB1 Transcription Factors
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / genetics
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Transcriptional Activation / genetics
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Up-Regulation / genetics
Substances
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DNA-Binding Proteins
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Homeodomain Proteins
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Nanog Homeobox Protein
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Nanog protein, mouse
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Octamer Transcription Factor-3
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Organic Cation Transport Proteins
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Pou5f1 protein, mouse
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SOXB1 Transcription Factors
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Sox2 protein, mouse
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Trans-Activators
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Transcription Factors
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solute carrier family 22 (organic cation transporter), member 3