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The pluripotency factor-bound intron 1 of Xist is dispensable for X chromosome inactivation and reactivation in vitro and in vivo.

TitleThe pluripotency factor-bound intron 1 of Xist is dispensable for X chromosome inactivation and reactivation in vitro and in vivo.
Publication TypeJournal Article
Year of Publication2013
AuthorsMinkovsky A, Barakat TStefan, Sellami N, Chin MHenry, Gunhanlar N, Gribnau J, Plath K
JournalCell Rep
Volume3
Issue3
Pagination905-18
Date Published2013 Mar 28
ISSN2211-1247
KeywordsAnimals, Cell Differentiation, Cellular Reprogramming, Embryonic Stem Cells, Gene Deletion, Gene Expression Regulation, Developmental, Introns, Mice, RNA, Long Noncoding, Transcription Factors, Transcription, Genetic, Up-Regulation, X Chromosome Inactivation
Abstract

X chromosome inactivation (XCI) is a dynamically regulated developmental process with inactivation and reactivation accompanying the loss and gain of pluripotency, respectively. A functional relationship between pluripotency and lack of XCI has been suggested, whereby pluripotency transcription factors repress the master regulator of XCI, the noncoding transcript Xist, by binding to its first intron (intron 1). To test this model, we have generated intron 1 mutant embryonic stem cells (ESCs) and two independent mouse models. We found that Xist's repression in ESCs, its transcriptional upregulation upon differentiation, and its silencing upon reprogramming to pluripotency are not dependent on intron 1. Although we observed subtle effects of intron 1 deletion on the randomness of XCI and in the absence of the antisense transcript Tsix in differentiating ESCs, these have little relevance in vivo because mutant mice do not deviate from Mendelian ratios of allele transmission. Altogether, our findings demonstrate that intron 1 is dispensable for the developmental dynamics of Xist expression.

DOI10.1016/j.celrep.2013.02.018
Alternate JournalCell Rep
PubMed ID23523354
PubMed Central IDPMC3615097
Grant ListAG039179 / AG / NIA NIH HHS / United States
DP2 OD001686 / OD / NIH HHS / United States
DP2OD001686 / OD / NIH HHS / United States
F30 AG039179 / AG / NIA NIH HHS / United States
P01 GM099134 / GM / NIGMS NIH HHS / United States
P01 GM099134 / GM / NIGMS NIH HHS / United States
P30 CA016042 / CA / NCI NIH HHS / United States
T32 GM008042 / GM / NIGMS NIH HHS / United States
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