The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome

Jesse M. Engreitz, Amy Pandya-Jones, Patrick McDonel, Alexander Shishkin, Klara Sirokman, Christine Surka, Sabah Kadri, Jeffrey Xing, Alon Goren, Eric S. Lander*, Kathrin Plath, Mitchell Guttman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

684 Scopus citations

Abstract

Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. We investigated the localization mechanisms of the Xist lncRNA during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X chromosome. Xist requires its silencing domain to spread across actively transcribed regions and thereby access the entire chromosome. These findings suggest a model in which Xist coats the X chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations.

Original languageEnglish (US)
Article number1237973
JournalScience
Volume341
Issue number6147
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • General

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