Perotti Irene, Broglia Laura, Tartaglia Gian Gaetano, Cerase Andrea
Unit of Cell and Developmental Biology, Department of Biology, Università di Pisa, Strada Statale dell'Abetone Brennero, 4, Pisa, 56123, Italy.
RNA Systems Biology Lab, Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen, 83, Genoa, 16152, Italy.
Genome Biol. 2025 Jul 21;26(1):215. doi: 10.1186/s13059-025-03666-8.
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.
X染色体失活（XCI）是雌性哺乳动物剂量补偿的关键机制，可确保仅一条X染色体上的基因得以表达，该过程通过长链非编码RNA Xist的表达启动。最近的证据强调了分子拥挤——很可能是通过液-液相分离（LLPS）——在形成由Xist RNA驱动的凝聚物中的重要性，这些凝聚物对于建立和维持沉默状态至关重要。通过整合现有知识和新出现的观点，我们对XCI的分子基础提供了全面的视角，并概述了基于LLPS的机制的操纵如何为新的治疗方法提供新途径。
