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

Author

Listed:
  • Emily Maclary

    (University of Michigan Medical School)

  • Emily Buttigieg

    (University of Michigan Medical School)

  • Michael Hinten

    (University of Michigan Medical School)

  • Srimonta Gayen

    (University of Michigan Medical School)

  • Clair Harris

    (University of Michigan Medical School)

  • Mrinal Kumar Sarkar

    (University of Michigan Medical School)

  • Sonya Purushothaman

    (Brody School of Medicine, East Carolina University)

  • Sundeep Kalantry

    (University of Michigan Medical School)

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.

Suggested Citation

  • Emily Maclary & Emily Buttigieg & Michael Hinten & Srimonta Gayen & Clair Harris & Mrinal Kumar Sarkar & Sonya Purushothaman & Sundeep Kalantry, 2014. "Differentiation-dependent requirement of Tsix long non-coding RNA in imprinted X-chromosome inactivation," Nature Communications, Nature, vol. 5(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5209
    DOI: 10.1038/ncomms5209
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    Cited by:

    1. Milan Kumar Samanta & Srimonta Gayen & Clair Harris & Emily Maclary & Yumie Murata-Nakamura & Rebecca M. Malcore & Robert S. Porter & Patricia M. Garay & Christina N. Vallianatos & Paul B. Samollow & , 2022. "Activation of Xist by an evolutionarily conserved function of KDM5C demethylase," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Marissa Cloutier & Surinder Kumar & Emily Buttigieg & Laura Keller & Brandon Lee & Aaron Williams & Sandra Mojica-Perez & Indri Erliandri & Andre Monteiro Da Rocha & Kenneth Cadigan & Gary D. Smith & , 2022. "Preventing erosion of X-chromosome inactivation in human embryonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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