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Science 321 (5896): 1693-1695

Copyright © 2008 by the American Association for the Advancement of Science

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*

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.

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.)

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