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Science (New York, N.Y.) DOI:10.1126/science.1237973

The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome.

Publication TypeJournal Article
Year of Publication2013
AuthorsEngreitz, JM, Pandya-Jones, A, McDonel, P, Shishkin, A, Sirokman, K, Surka, C, Kadri, S, Xing, J, Goren, A, Lander, ES, Plath, K, Guttman, M
JournalScience (New York, N.Y.)
Date Published2013/07/04

Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. Here, we investigate 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. This suggests a model where Xist coats the X-chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations.