No abstract

No abstract

Since publication of the original article, we have become aware of three errors in our paper that we are now correcting. (1) The author list omitted Joanna W. Jachowicz and Mackenzie Strehle. They contributed the initial observation that the intrinsically disordered region of SPEN is critical for silencing some genes on the X chromosome, and we are now including them as authors. The author list, affiliations, and author contributions have been updated online, and all co-authors have approved the changes. (2) We have added a new reference and citations to Jachowicz et al. ( 2021), which reports on how SPEN/SHARP mediates X-restricted, Xistdependent silencing. (3) In the "SMACs are the functional units of Xist-mediated XCI" section of the discussion, the molecular weight of SPEN was incorrectly reported as "500 KDa" instead of the correct value of "400 KDa" in the sentence "Each Xist-SMAC accumulates 35 copies of the 500 KDa protein SPEN." These changes have now been corrected online, and the authors apologize for any confusion.

The long non-coding RNA Xist exploits numerous effector proteins to progressively induce gene silencing across the X chromosome and form the inactive X (Xi)-compartment. The mechanism underlying formation of the chromosome-wide Xi-compartment is poorly understood. Here, we find that formation of the Xi-compartment is induced by ∼50 locally confined granules, where two Xist RNA molecules nucleate supra-molecular complexes (SMCs) of interacting proteins. Xist-SMCs are transient structures that concentrate rapidly recycling proteins in the X by increasing protein binding affinity. We find that gene silencing originates at Xist-SMCs and propagates across the entire chromosome over time, achieved by Polycomb-mediated coalescence of chromatin regions and aggregation, via its intrinsically disordered domains, of the critical silencing factor SPEN. Our results suggest a new model for X chromosome inactivation, in which Xist RNA induces macromolecular crowding of heterochromatinizing proteins near distinct sites which ultimately increases their density throughout the chromosome. This mechanism enables deterministic gene silencing without the need for Xist ribonucleoprotein complex-chromatin interactions at each target gene.