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<p>X-chromosome inactivation (XCI) is a crucial mechanism of dosage compensation in female mammals ensuring that genes from only one X chromosome are expressed, initiated through expression of the long noncoding RNA <i>Xist</i>. Recent evidence underscores the significance of molecular crowding—most likely via liquid–liquid phase separation (LLPS)—in forming <i>Xist</i> RNA-driven condensates critical for establishing and sustaining the silenced state. By integrating existing knowledge and emerging ideas, we provide a comprehensive perspective on the molecular underpinnings of XCI and outline how manipulation of LLPS-based mechanisms offers new avenues for novel therapeutic approaches.</p>

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Xist condensates: perspectives for therapeutic intervention

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月21日

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  • Irene Perotti,
  • Laura Broglia,
  • Gian Gaetano Tartaglia,
  • Andrea Cerase

摘要

X-chromosome inactivation (XCI) is a crucial mechanism of dosage compensation in female mammals ensuring that genes from only one X chromosome are expressed, initiated through expression of the long noncoding RNA Xist. Recent evidence underscores the significance of molecular crowding—most likely via liquid–liquid phase separation (LLPS)—in forming Xist RNA-driven condensates critical for establishing and sustaining the silenced state. By integrating existing knowledge and emerging ideas, we provide a comprehensive perspective on the molecular underpinnings of XCI and outline how manipulation of LLPS-based mechanisms offers new avenues for novel therapeutic approaches.