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Article Dans Une Revue Nature Structural and Molecular Biology Année : 2024

XIST dampens X chromosome activity in a SPEN-dependent manner during early human development

Charbel Alfeghaly
Gaël Castel
Emmanuel Cazottes
Madeleine Moscatelli
  • Fonction : Auteur
Eva Moinard
Miguel Casanova
  • Fonction : Auteur
Juliette Boni
  • Fonction : Auteur
Kasturi Mahadik
  • Fonction : Auteur
Jenna Lammers
  • Fonction : Auteur
Thomas Freour
Louis Chauviere
  • Fonction : Auteur
Carla Piqueras
  • Fonction : Auteur
Ruben Boers
  • Fonction : Auteur
Joachim Boers
  • Fonction : Auteur
Joost Gribnau
Laurent David
  • Fonction : Auteur
Jean-François Ouimette
  • Fonction : Auteur

Résumé

Abstract XIST (X-inactive specific transcript) long noncoding RNA (lncRNA) is responsible for X chromosome inactivation (XCI) in placental mammals, yet it accumulates on both X chromosomes in human female preimplantation embryos without triggering X chromosome silencing. The XACT (X-active coating transcript) lncRNA coaccumulates with XIST on active X chromosomes and may antagonize XIST function. Here, we used human embryonic stem cells in a naive state of pluripotency to assess the function of XIST and XACT in shaping the X chromosome chromatin and transcriptional landscapes during preimplantation development. We show that XIST triggers the deposition of polycomb-mediated repressive histone modifications and dampens the transcription of most X-linked genes in a SPEN-dependent manner, while XACT deficiency does not significantly affect XIST activity or X-linked gene expression. Our study demonstrates that XIST is functional before XCI, confirms the existence of a transient process of X chromosome dosage compensation and reveals that XCI and dampening rely on the same set of factors.

Dates et versions

hal-04651665 , version 1 (17-07-2024)

Identifiants

Citer

Charbel Alfeghaly, Gaël Castel, Emmanuel Cazottes, Madeleine Moscatelli, Eva Moinard, et al.. XIST dampens X chromosome activity in a SPEN-dependent manner during early human development. Nature Structural and Molecular Biology, 2024, ⟨10.1038/s41594-024-01325-3⟩. ⟨hal-04651665⟩

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