Journal Article

A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation

Lee, Jeannie T., Kesner, Barry, Boukhali, Myriam, Lessing, Derek, Wei, Chunyao, Colognori, David, Minajigi, Anand, Sunwoo, Hongjae, Haas, Wilhelm, Payer, Bernhard, Froberg, John E.

2015

Overview

Female mammals have two X chromosomes, one of which is almost completely shut down during development. The long noncoding Xist RNA plays a role in this process. To understand how a whole chromosome can be stably inactivated, Minajigi et al. identified many of the proteins that bind to the Xist RNA, which include cohesins. Paradoxically, the interaction between Xist and cohesin subunits resulted in repulsion of cohesin complexes from the inactive X chromosome, changing the three-dimensional shape of the whole chromosome. Science , this issue 10.1126/science.aab2276 A screen for factors that bind directly to RNA reveals the proteins that interact with the long noncoding RNA Xist. The inactive X chromosome (Xi) serves as a model to understand gene silencing on a global scale. Here, we perform “identification of direct RNA interacting proteins” (iDRiP) to isolate a comprehensive protein interactome for Xist, an RNA required for Xi silencing. We discover multiple classes of interactors—including cohesins, condensins, topoisomerases, RNA helicases, chromatin remodelers, and modifiers—that synergistically repress Xi transcription. Inhibiting two or three interactors destabilizes silencing. Although Xist attracts some interactors, it repels architectural factors. Xist evicts cohesins from the Xi and directs an Xi-specific chromosome conformation. Upon deleting Xist , the Xi acquires the cohesin-binding and chromosomal architecture of the active X. Our study unveils many layers of Xi repression and demonstrates a central role for RNA in the topological organization of mammalian chromosomes.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Chromosomes / Cohesion / Epigenetics / Females / Genes / Inhibition / Mammals / Proteins / RESEARCH ARTICLE SUMMARY / Ribonucleic acid / Ribonucleic acids / RNA / Shutdowns / Three dimensional models