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Science 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
Date Published2013 Aug 16
KeywordsAnimals, Cell Differentiation, Cell Line, Chromatin, Female, Genome, Male, Mice, Models, Genetic, RNA, Long Noncoding, Transcription, Genetic, X Chromosome, X Chromosome Inactivation

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.


Alternate JournalScience
PubMed ID23828888
PubMed Central IDPMC3778663
Grant List1F32GM103139-01 / GM / NIGMS NIH HHS / United States
F32 GM103139 / GM / NIGMS NIH HHS / United States
DP5OD012190 / OD / NIH HHS / United States
P01 GM099134 / GM / NIGMS NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
P01GM099134 / GM / NIGMS NIH HHS / United States
P50HG006193 / HG / NHGRI NIH HHS / United States
DP5 OD012190 / OD / NIH HHS / United States