title: The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome.
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.
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Engreitz
authors.forename: Amy
authors.initials: A
authors.lastname: Pandya-Jones
authors.forename: Patrick
authors.initials: P
authors.lastname: McDonel
authors.forename: Alexander
authors.initials: A
authors.lastname: Shishkin
authors.forename: Klara
authors.initials: K
authors.lastname: Sirokman
authors.forename: Christine
authors.initials: C
authors.lastname: Surka
authors.forename: Sabah
authors.initials: S
authors.lastname: Kadri
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Xing
authors.forename: Alon
authors.initials: A
authors.lastname: Goren
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Kathrin
authors.initials: K
authors.lastname: Plath
authors.forename: Mitchell
authors.initials: M
authors.lastname: Guttman
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D005260:Female; D016678:Genome; D008297:Male; D051379:Mice; D008957:Models, Genetic; D062085:RNA, Long Noncoding / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D014960:X Chromosome / Q000378:metabolism* / Q000648:ultrastructure; D049951:X Chromosome Inactivation
chemical_list: D002843:Chromatin; D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA