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The Polycomb-repressive complexes PRC1 and PRC2 play a key role in chromosome silencing induced by the non-coding RNA Xist. Polycomb recruitment is initiated by the PCGF3/5-PRC1 complex, which catalyzes chromosome-wide H2A lysine 119 ubiquitylation, signaling recruitment of other PRC1 complexes, and PRC2. However, the molecular mechanism for PCGF3/5-PRC1 recruitment by Xist RNA is not understood. Here we define the Xist RNA Polycomb Interaction Domain (XR-PID), a 600 nt sequence encompassing the Xist B-repeat element. Deletion of XR-PID abolishes Xist-dependent Polycomb recruitment, in turn abrogating Xist-mediated gene silencing and reversing Xist-induced chromatin inaccessibility. We identify the RNA-binding protein hnRNPK as the principal XR-PID binding factor required to recruit PCGF3/5-PRC1. Accordingly, synthetically tethering hnRNPK to Xist RNA lacking XR-PID is sufficient for Xist-dependent Polycomb recruitment. Our findings define a key pathway for Polycomb recruitment by Xist RNA, providing important insights into mechanisms of chromatin modification by non-coding RNA.

Original publication

DOI

10.1016/j.molcel.2017.11.013

Type

Journal article

Journal

Mol Cell

Publication Date

07/12/2017

Volume

68

Pages

955 - 969.e10

Keywords

Animals, Binding Sites, Cell Line, Embryonic Stem Cells, Histones, Lysine, Mice, Polycomb Repressive Complex 1, Polycomb-Group Proteins, Protein Binding, Protein Interaction Domains and Motifs, RNA Interference, RNA, Long Noncoding, Ribonucleoproteins, Transcription, Genetic, Transfection, Ubiquitination, X Chromosome, X Chromosome Inactivation