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Nat Commun. 2014 Jun 30;5:4209. doi: 10.1038/ncomms5209.

Differentiation-dependent requirement of Tsix long non-coding RNA in imprinted X-chromosome inactivation.

Author information

  • 1Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA.
  • 2Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.

Abstract

Imprinted X-inactivation is a paradigm of mammalian transgenerational epigenetic regulation resulting in silencing of genes on the paternally inherited X-chromosome. The preprogrammed fate of the X-chromosomes is thought to be controlled in cis by the parent-of-origin-specific expression of two opposing long non-coding RNAs, Tsix and Xist, in mice. Exclusive expression of Tsix from the maternal-X has implicated it as the instrument through which the maternal germline prevents inactivation of the maternal-X in the offspring. Here, we show that Tsix is dispensable for inhibiting Xist and X-inactivation in the early embryo and in cultured stem cells of extra-embryonic lineages. Tsix is instead required to prevent Xist expression as trophectodermal progenitor cells differentiate. Despite induction of wild-type Xist RNA and accumulation of histone H3-K27me3, many Tsix-mutant X-chromosomes fail to undergo ectopic X-inactivation. We propose a novel model of lncRNA function in imprinted X-inactivation that may also apply to other genomically imprinted loci.

PMID:
24979243
PMCID:
PMC4086345
DOI:
10.1038/ncomms5209
[PubMed - indexed for MEDLINE]
Free PMC Article
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