Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Rep. 2013 Mar 28;3(3):905-18. doi: 10.1016/j.celrep.2013.02.018. Epub 2013 Mar 21.

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

Author information

1
Department of Biological Chemistry, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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.

PMID:
23523354
PMCID:
PMC3615097
DOI:
10.1016/j.celrep.2013.02.018
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center