Pintacuda, G. et al. (2017) hnRNPK recruits PCGF3/5-PRC1 to the Xist RNA B-repeat to establish polycomb-mediated chromosomal silencing. Molecular Cell, 68(5), 955-969.e10. (doi: 10.1016/j.molcel.2017.11.013) (PMID:29220657) (PMCID:PMC5735038)
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Abstract
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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Castello, Professor Alfredo |
Authors: | Pintacuda, G., Wei, G., Roustan, C., Kirmizitas, B. A., Solcan, N., Cerase, A., Castello, A., Mohammed, S., Moindrot, B., Nesterova, T. B., and Brockdorff, N. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
Journal Name: | Molecular Cell |
Publisher: | Elsevier (Cell Press) |
ISSN: | 1097-2765 |
ISSN (Online): | 1097-4164 |
Copyright Holders: | Copyright © 2017 The Authors |
First Published: | First published in Molecular Cell 68(5): 955-969.e10 |
Publisher Policy: | Reproduced under a Creative Commons License |
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