Title | The pluripotency factor-bound intron 1 of Xist is dispensable for X chromosome inactivation and reactivation in vitro and in vivo. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Minkovsky A, Barakat TStefan, Sellami N, Chin MHenry, Gunhanlar N, Gribnau J, Plath K |
Journal | Cell Rep |
Volume | 3 |
Issue | 3 |
Pagination | 905-18 |
Date Published | 2013 Mar 28 |
ISSN | 2211-1247 |
Keywords | Animals, 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. |
DOI | 10.1016/j.celrep.2013.02.018 |
Alternate Journal | Cell Rep |
PubMed ID | 23523354 |
PubMed Central ID | PMC3615097 |
Grant List | AG039179 / 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 |