Molecular coupling of Xist regulation and pluripotency.
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.
Navarro
Pablo
P
Institut Pasteur, Unité de Génétique Moléculaire Murine, CNRS, URA2578, F-75015, Paris, France.
Chambers
Ian
I
Karwacki-Neisius
Violetta
V
Chureau
Corinne
C
Morey
Céline
C
Rougeulle
Claire
C
Avner
Philip
P
D000818:Animals; D053624:Blastocyst Inner Cell Mass / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D024002:HMGB Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007438:Introns; D008297:Male; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation; D014960:X Chromosome / Q000502:physiology; D049951:X Chromosome Inactivation
D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; C077885:XIST non-coding RNA