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

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 th...

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Veröffentlicht in:Science (American Association for the Advancement of Science) 2013-08, Vol.341 (6147), p.1237973-1237973
Hauptverfasser: Engreitz, Jesse M, Pandya-Jones, Amy, McDonel, Patrick, Shishkin, Alexander, Sirokman, Klara, Surka, Christine, Kadri, Sabah, Xing, Jeffrey, Goren, Alon, Lander, Eric S, Plath, Kathrin, Guttman, Mitchell
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container_end_page 1237973
container_issue 6147
container_start_page 1237973
container_title Science (American Association for the Advancement of Science)
container_volume 341
creator Engreitz, Jesse M
Pandya-Jones, Amy
McDonel, Patrick
Shishkin, Alexander
Sirokman, Klara
Surka, Christine
Kadri, Sabah
Xing, Jeffrey
Goren, Alon
Lander, Eric S
Plath, Kathrin
Guttman, Mitchell
description 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.
doi_str_mv 10.1126/science.1237973
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subjects Animals
Cell Differentiation
Cell Line
Chromatin - chemistry
Chromatin - metabolism
Chromosomes
Female
Females
Genes
Genome
Genomes
Government regulations
Inactivation
Male
Mice
Models, Genetic
Ribonucleic acids
RNA, Long Noncoding - chemistry
RNA, Long Noncoding - metabolism
Three dimensional
Transcription, Genetic
X Chromosome - metabolism
X Chromosome - ultrastructure
X Chromosome Inactivation
title The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome
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