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 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.
|Year of Publication||
2013 Aug 16
|PubMed Central ID||
1F32GM103139-01 / 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