PT  - JOURNAL ARTICLE
AU  - Amy Pandya-Jones
AU  - Yolanda Markaki
AU  - Jacques Serizay
AU  - Tsotne Chitiashvilli
AU  - Walter Mancia
AU  - Andrey Damianov
AU  - Costantinos Chronis
AU  - Bernadett Papp
AU  - Chun-Kan Chen
AU  - Robin McKee
AU  - Xiao-Jun Wang
AU  - Anthony Chau
AU  - Heinrich Leonhardt
AU  - Sika Zheng
AU  - Mitchell Guttman
AU  - Douglas L. Black
AU  - Kathrin Plath
TI  - An <em>Xist</em>-dependent protein assembly mediates <em>Xist</em> localization and gene silencing
AID  - 10.1101/2020.03.09.979369
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.09.979369
4099  - http://biorxiv.org/content/early/2020/03/12/2020.03.09.979369.short
4100  - http://biorxiv.org/content/early/2020/03/12/2020.03.09.979369.full
AB  - Nuclear compartments play diverse roles in regulating gene expression, yet the molecular forces and components driving compartment formation are not well understood. Studying how the lncRNA Xist establishes the inactive-X-chromosome (Xi)-compartment, we found that the Xist RNA-binding-proteins PTBP1, MATR3, TDP43, and CELF1 form a condensate to create an Xi-domain that can be sustained in the absence of Xist. The E-repeat-sequence of Xist serves a multivalent binding-platform for these proteins. Without the E-repeat, Xist initially coats the X-chromosome during XCI onset but subsequently disperses across the nucleus with loss of gene silencing. Recruitment of PTBP1, MATR3, TDP-43 or CELF1 to ΔE-Xist rescues these phenotypes, and requires both self-association of MATR3 and TDP-43 and a heterotypic PTBP1-MATR3-interaction. Together, our data reveal that Xist sequesters itself within the Xi-territory and perpetuates gene silencing by seeding a protein-condensate. Our findings uncover an unanticipated mechanism for epigenetic memory and elucidate the interplay between RNA and RNA-binding-proteins in creating compartments for gene regulation.