A protein assembly mediates Xist localization and gene silencing

Amy Pandya-Jones, Yolanda Markaki, Jacques Serizay, Tsotne Chitiashvili, Walter R. Mancia Leon, Andrey Damianov, Constantinos Chronis, Bernadett Papp, Chun-Kan Chen, Robin McKee, Xiao-Jun Wang, Anthony Chau, Shan Sabri, Heinrich Leonhardt, Sika Zheng, Mitchell Guttman, Douglas. L. Black () and Kathrin Plath ()
Additional contact information
Amy Pandya-Jones: University of California Los Angeles
Yolanda Markaki: University of California Los Angeles
Jacques Serizay: University of California Los Angeles
Tsotne Chitiashvili: University of California Los Angeles
Walter R. Mancia Leon: University of California Los Angeles
Andrey Damianov: University of California Los Angeles
Constantinos Chronis: University of California Los Angeles
Bernadett Papp: University of California Los Angeles
Chun-Kan Chen: California Institute of Technology
Robin McKee: University of California Los Angeles
Xiao-Jun Wang: University of California Los Angeles
Anthony Chau: University of California Los Angeles
Shan Sabri: University of California Los Angeles
Heinrich Leonhardt: Department of Biology and Center for Integrated Protein Science, LMU Munich
Sika Zheng: University of California Los Angeles
Mitchell Guttman: California Institute of Technology
Douglas. L. Black: University of California Los Angeles
Kathrin Plath: University of California Los Angeles

Nature, 2020, vol. 587, issue 7832, 145-151

Abstract: Abstract Nuclear compartments have diverse roles in regulating gene expression, yet the molecular forces and components that drive compartment formation remain largely unclear1. The long non-coding RNA Xist establishes an intra-chromosomal compartment by localizing at a high concentration in a territory spatially close to its transcription locus2 and binding diverse proteins3–5 to achieve X-chromosome inactivation (XCI)6,7. The XCI process therefore serves as a paradigm for understanding how RNA-mediated recruitment of various proteins induces a functional compartment. The properties of the inactive X (Xi)-compartment are known to change over time, because after initial Xist spreading and transcriptional shutoff a state is reached in which gene silencing remains stable even if Xist is turned off8. Here we show that the Xist RNA-binding proteins PTBP19, MATR310, TDP-4311 and CELF112 assemble on the multivalent E-repeat element of Xist7 and, via self-aggregation and heterotypic protein–protein interactions, form a condensate1 in the Xi. This condensate is required for gene silencing and for the anchoring of Xist to the Xi territory, and can be sustained in the absence of Xist. Notably, these E-repeat-binding proteins become essential coincident with transition to the Xist-independent XCI phase8, indicating that the condensate seeded by the E-repeat underlies the developmental switch from Xist-dependence to Xist-independence. Taken together, our data show that Xist forms the Xi compartment by seeding a heteromeric condensate that consists of ubiquitous RNA-binding proteins, revealing an unanticipated mechanism for heritable gene silencing.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2703-0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:587:y:2020:i:7832:d:10.1038_s41586-020-2703-0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2703-0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().