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

A new science paper from Eric Lander’s lab came out on Xist lncRNA.

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.