Leading science, pioneering therapies
CRM Publications

Molecular coupling of Xist regulation and pluripotency.

TitleMolecular coupling of Xist regulation and pluripotency.
Publication TypeJournal Article
Year of Publication2008
AuthorsNavarro P, Chambers I, Karwacki-Neisius V, Chureau C, Morey C, Rougeulle C, Avner P
Date Published2008 Sep 19
KeywordsAnimals, Blastocyst Inner Cell Mass, Cell Differentiation, Cell Line, DNA-Binding Proteins, Embryonic Stem Cells, Female, HMGB Proteins, Homeodomain Proteins, Introns, Male, Mice, Octamer Transcription Factor-3, Pluripotent Stem Cells, RNA, Long Noncoding, RNA, Untranslated, SOXB1 Transcription Factors, Transcription Factors, Up-Regulation, X Chromosome, X Chromosome Inactivation

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.

Alternate JournalScience
PubMed ID18802003
Grant List / / Biotechnology and Biological Sciences Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom