期刊
SCIENCE
卷 349, 期 6245, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aab2276
关键词
-
资金
- NIH [R01-DA-38695, R03-MH97478]
- Rett Syndrome Research Trust
- International Rett Syndrome Foundation
- National Science Foundation
- MGH Fund for Medical Discovery
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.
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