Abstract
During mouse embryogenesis, reversion of imprinted X chromosome inactivation in the pluripotent inner cell mass of the female blastocyst is initiated by the repression of Xist from the paternal X chromosome. Here we report that key factors supporting pluripotency-Nanog, Oct3/4, and Sox2-bind within Xist intron 1 in undifferentiated embryonic stem (ES) cells. Whereas Nanog null ES cells display a reversible and moderate up-regulation of Xist in the absence of any apparent modification of Oct3/4 and Sox2 binding, the drastic release of all three factors from Xist intron 1 triggers rapid ectopic accumulation of Xist RNA. We conclude that the three main genetic factors underlying pluripotency cooperate to repress Xist and thus couple X inactivation reprogramming to the control of pluripotency during embryogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blastocyst Inner Cell Mass / metabolism
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Cell Differentiation
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Cell Line
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DNA-Binding Proteins / metabolism*
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Embryonic Stem Cells / cytology
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Embryonic Stem Cells / metabolism*
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Female
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HMGB Proteins / metabolism*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Introns
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Male
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Mice
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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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Pluripotent Stem Cells / cytology
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Pluripotent Stem Cells / metabolism*
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RNA, Long Noncoding
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RNA, Untranslated / genetics*
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RNA, Untranslated / metabolism
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SOXB1 Transcription Factors
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Transcription Factors / metabolism*
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Up-Regulation
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X Chromosome / physiology
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X Chromosome Inactivation*
Substances
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DNA-Binding Proteins
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HMGB 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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Pou5f1 protein, mouse
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RNA, Long Noncoding
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RNA, Untranslated
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SOXB1 Transcription Factors
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Sox2 protein, mouse
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Transcription Factors
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XIST non-coding RNA