A Primary Role for the Tsix lncRNA in Maintaining Random X-Chromosome Inactivation

Srimonta Gayen, Emily Maclary, Emily Buttigieg, Michael Hinten, Sundeep Kalantry

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Differentiating pluripotent epiblast cells in eutherians undergo random X-inactivation, which equalizes X-linked gene expression between the sexes by silencing one of the two X-chromosomes in females. Tsix RNA is believed to orchestrate the initiation ofX-inactivation, influencing the choice of which Xremains active by preventing expression of the antisense Xist RNA, which is required to silence the inactive-X. Here we profile X-chromosome activity in Tsix-mutant (XδTsix) mouse embryonic epiblasts, epiblast stem cells, and embryonic stem cells. Unexpectedly, we find that Xist is stably repressed on the XδTsix in both sexes in undifferentiated epiblast cells invivo and invitro, resulting in stochastic X-inactivation in females despite Tsix-heterozygosity. Tsix is instead required to silence Xist on the active-X as epiblast cells differentiate in both males and females. Thus, Tsix is not required at the onset of random X-inactivation; instead, it protects the active-X from ectopic silencing once X-inactivation has commenced.

Original languageEnglish (US)
Pages (from-to)1251-1265
Number of pages15
JournalCell Reports
Volume11
Issue number8
DOIs
StatePublished - May 26 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'A Primary Role for the Tsix lncRNA in Maintaining Random X-Chromosome Inactivation'. Together they form a unique fingerprint.

Cite this