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Science. 2015 Jul 17;349(6245). doi: 10.1126/science.aab2276 aab2276. Epub 2015 Jun 18.

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

Author information

1
Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA USA; Department of Genetics, Harvard Medical School, Boston, MA, USA.
2
Massachusetts General Hospital Cancer Center, Charlestown, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
#
Contributed equally

Abstract

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.

PMID:
26089354
PMCID:
PMC4845908
DOI:
10.1126/science.aab2276
[Indexed for MEDLINE]
Free PMC Article

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