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.

Automated summary

This study reveals the molecular mechanisms through which the long non-coding RNA Xist silences genes on the entire X chromosome. By forming dimeric foci, Xist seeds the formation of large protein assemblies that contain various proteins, including SPEN, CIZ1, CELF, PTBP1, and components of Polycomb repressive complexes 1 and 2. These protein assemblies extend spatially beyond each Xist focus, explaining how this long non-coding RNA triggers silencing across the entire chromosome.