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<p>Random X-chromosome inactivation is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long noncoding RNA Xist, occurs in the early embryo and is stably maintained throughout life, although inactivation is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling on developing mouse PGCs, we provide a detailed map of X-linked gene reactivation. Despite the absence of Xist expression, PGCs still harbor a fully silent X chromosome at embryonic day 9.5 (E9.5). Subsequently, X-linked genes undergo gradual and distinct regional reactivation. At E12.5, a substantial part of the inactive X chromosome resists reactivation, retaining an epigenetic memory of its silencing. Our findings define the orchestration of reactivation of the inactive X chromosome, a key event in female PGC reprogramming with direct implications for reproduction.</p>

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Temporal and regional X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing

  • 期刊论文

  • 发表日期：

    2025年1月21日

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  • Clara Roidor,
  • Laurène Syx,
  • Emmanuelle Beyne,
  • Peggy Raynaud,
  • Dina Zielinski,
  • Aurélie Teissandier,
  • Caroline Lee,
  • Marius Walter,
  • Nicolas Servant,
  • Karim Chebli,
  • Deborah Bourc’his,
  • M. Azim Surani,
  • Maud Borensztein

摘要

Random X-chromosome inactivation is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long noncoding RNA Xist, occurs in the early embryo and is stably maintained throughout life, although inactivation is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling on developing mouse PGCs, we provide a detailed map of X-linked gene reactivation. Despite the absence of Xist expression, PGCs still harbor a fully silent X chromosome at embryonic day 9.5 (E9.5). Subsequently, X-linked genes undergo gradual and distinct regional reactivation. At E12.5, a substantial part of the inactive X chromosome resists reactivation, retaining an epigenetic memory of its silencing. Our findings define the orchestration of reactivation of the inactive X chromosome, a key event in female PGC reprogramming with direct implications for reproduction.