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

Emily Maclary, Emily Buttigieg, Michael Hinten, Srimonta Gayen, Clair Harris, Mrinal Kumar Sarkar, Sonya Purushothaman, Sundeep Kalantry

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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.

Original languageEnglish (US)
Article number4209
JournalNature communications
StatePublished - Jun 30 2014
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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