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Phase separation drives X-chromosome inactivation

The molecular mechanisms by which a few molecules of the long non-coding RNA Xist silence genes on the entire X chromosome are poorly understood. New evidence suggests that dimeric foci of Xist seed the formation of large protein assemblies that contain a wide spectrum of proteins, such as SPEN (SHARP), CIZ1, CELF, PTBP1 and components of Polycomb repressive complexes 1 and 2. These assemblies, each of which may contain hundreds to thousands of molecules of proteins, extend spatially beyond each focus of Xist, which explains how this long non-coding RNA triggers silencing across an entire chromosome.

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Fig. 1: Xist condensates on the Xi generate gradients of repressors that silence Xist-proximal and distant genes on the whole X chromosome.


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A.C. has been funded by a grant from the Rett Syndrome Research Trust, two grants from BARTS Charity and intramural support from QMUL and University of Pisa. G.G.T. is supported by European Research Council (RIBOMYLOME 309545 and ASTRA 855923), the Spanish Ministry of Economy and Competitiveness (BFU2017-86970-P) and H2020 projects (IASIS 727658 and INFORE 825080).

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Correspondence to Andrea Cerase, J. Mauro Calabrese or Gian Gaetano Tartaglia.

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Cerase, A., Calabrese, J.M. & Tartaglia, G.G. Phase separation drives X-chromosome inactivation. Nat Struct Mol Biol 29, 183–185 (2022).

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