Spatio-temporal X-linked gene reactivation and site-specific retention of epigenetic silencing in the mouse germline - Archive ouverte HAL Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2023

Spatio-temporal X-linked gene reactivation and site-specific retention of epigenetic silencing in the mouse germline

Laurène Syx
  • Fonction : Auteur
Emmanuelle Beyne
  • Fonction : Auteur
Dina Zielinski
  • Fonction : Auteur
Aurélie Teissandier
  • Fonction : Auteur
Caroline Lee
  • Fonction : Auteur
Marius Walter
  • Fonction : Auteur
Nicolas Servant
  • Fonction : Auteur
Karim Chebli
  • Fonction : Auteur
Déborah Bourc’his
  • Fonction : Auteur
M. Azim Surani
  • Fonction : Auteur

Résumé

Abstract Random X-chromosome inactivation (XCI) is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long non-coding RNA Xist , occurs in the epiblast and is stably maintained to ensure proper dosage compensation of X-linked genes during life. However, this silencing is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling in developing in vivo PGC, we provide unprecedented detailed maps of gene reactivation. We demonstrated that PGC still carry a fully silent X chromosome on embryonic day (E) 9.5, despite the loss of Xist expression. X-linked genes are then gradually reactivated outside the Xist first-bound regions. At E12.5, a significant part of the inactive X chromosome (Xi) still resists reactivation, carrying an epigenetic memory of its silencing. Late-reactivated genes are enriched in repressive chromatin marks, including DNA methylation and H3K27me3 marks. Our results define the timing of reactivation of the silent X chromosome a key event in female PGC reprogramming with direct implications for reproduction.
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Dates et versions

hal-04266626 , version 1 (02-11-2023)

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Clara Roidor, Laurène Syx, Emmanuelle Beyne, Dina Zielinski, Aurélie Teissandier, et al.. Spatio-temporal X-linked gene reactivation and site-specific retention of epigenetic silencing in the mouse germline. 2023. ⟨hal-04266626⟩
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