Xist condensates: perspectives for therapeutic intervention

Abstract 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...

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Main Authors: Irene Perotti, Laura Broglia, Gian Gaetano Tartaglia, Andrea Cerase
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Genome Biology
Subjects:
Online Access:https://doi.org/10.1186/s13059-025-03666-8
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author Irene Perotti
Laura Broglia
Gian Gaetano Tartaglia
Andrea Cerase
author_facet Irene Perotti
Laura Broglia
Gian Gaetano Tartaglia
Andrea Cerase
author_sort Irene Perotti
collection DOAJ
description Abstract 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.
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institution Kabale University
issn 1474-760X
language English
publishDate 2025-07-01
publisher BMC
record_format Article
series Genome Biology
spelling doaj-art-e70726bd5bdc4a8fbe8b39a1e22383d12025-08-20T03:46:07ZengBMCGenome Biology1474-760X2025-07-0126113510.1186/s13059-025-03666-8Xist condensates: perspectives for therapeutic interventionIrene Perotti0Laura Broglia1Gian Gaetano Tartaglia2Andrea Cerase3Unit of Cell and Developmental Biology, Department of Biology, Università di Pisa, Strada Statale dell’Abetone Brennero, 4RNA Systems Biology Lab, Center for Human Technologies, Istituto Italiano di TecnologiaRNA Systems Biology Lab, Center for Human Technologies, Istituto Italiano di TecnologiaUnit of Cell and Developmental Biology, Department of Biology, Università di Pisa, Strada Statale dell’Abetone Brennero, 4Abstract 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.https://doi.org/10.1186/s13059-025-03666-8XistX-chromosome inactivationLiquid-liquid phase separationX-reactivationX-linked disordersRNA-binding proteins
spellingShingle Irene Perotti
Laura Broglia
Gian Gaetano Tartaglia
Andrea Cerase
Xist condensates: perspectives for therapeutic intervention
Genome Biology
Xist
X-chromosome inactivation
Liquid-liquid phase separation
X-reactivation
X-linked disorders
RNA-binding proteins
title Xist condensates: perspectives for therapeutic intervention
title_full Xist condensates: perspectives for therapeutic intervention
title_fullStr Xist condensates: perspectives for therapeutic intervention
title_full_unstemmed Xist condensates: perspectives for therapeutic intervention
title_short Xist condensates: perspectives for therapeutic intervention
title_sort xist condensates perspectives for therapeutic intervention
topic Xist
X-chromosome inactivation
Liquid-liquid phase separation
X-reactivation
X-linked disorders
RNA-binding proteins
url https://doi.org/10.1186/s13059-025-03666-8
work_keys_str_mv AT ireneperotti xistcondensatesperspectivesfortherapeuticintervention
AT laurabroglia xistcondensatesperspectivesfortherapeuticintervention
AT giangaetanotartaglia xistcondensatesperspectivesfortherapeuticintervention
AT andreacerase xistcondensatesperspectivesfortherapeuticintervention