Molecular Coupling of Xist Regulation and Pluripotency
Pablo Navarro,1
Ian Chambers,2
Violetta Karwacki-Neisius,2
Corinne Chureau,1
Céline Morey,1
Claire Rougeulle,1*
Philip Avner1*
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.
1 Institut Pasteur, Unité de Génétique Moléculaire Murine, CNRS, URA2578, F-75015, Paris, France.
2 Medical Research Council (MRC) Centre Development in Stem Cell Biology, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, MRC EH9 3JQ, Edinburgh, UK.
* To whom correspondence should be addressed. E-mail: rougeull{at}pasteur.fr (C.R.); pavner{at}pasteur.fr (P.A.)
