Gene Silencing Triggers Polycomb Repressive Complex 2 Recruitment to CpG Islands Genome Wide

TY - JOUR

T1 - Gene Silencing Triggers Polycomb Repressive Complex 2 Recruitment to CpG Islands Genome Wide

AU - Riising, Eva Madi

AU - Vacher-Comet, Itys

AU - Leblanc, Benjamin Olivier

AU - Wu, Xudong

AU - Johansen, Jens Vilstrup

AU - Helin, Kristian

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/8/7

Y1 - 2014/8/7

N2 - Polycomb group (PcG) proteins are required for normal differentiation and development and are frequently deregulated in cancer. PcG proteins are involved in gene silencing; however, their role in initiation and maintenance of transcriptional repression is not well defined. Here, we show that knockout of the Polycomb repressive complex 2 (PRC2) does not lead to significant gene expression changes in mouse embryonic stem cells (mESCs) and that it is dispensable for initiating silencing of target genes during differentiation. Transcriptional inhibition in mESCs is sufficient to induce genome-wide ectopic PRC2 recruitment to endogenous PcG target genes found in other tissues. PRC2 binding analysis shows that it is restricted to nucleosome-free CpG islands (CGIs) of untranscribed genes. Our results show that it is the transcriptional state that governs PRC2 binding, and we propose that it binds by default to nontranscribed CGI genes to maintain their silenced state and to protect cell identity.

AB - Polycomb group (PcG) proteins are required for normal differentiation and development and are frequently deregulated in cancer. PcG proteins are involved in gene silencing; however, their role in initiation and maintenance of transcriptional repression is not well defined. Here, we show that knockout of the Polycomb repressive complex 2 (PRC2) does not lead to significant gene expression changes in mouse embryonic stem cells (mESCs) and that it is dispensable for initiating silencing of target genes during differentiation. Transcriptional inhibition in mESCs is sufficient to induce genome-wide ectopic PRC2 recruitment to endogenous PcG target genes found in other tissues. PRC2 binding analysis shows that it is restricted to nucleosome-free CpG islands (CGIs) of untranscribed genes. Our results show that it is the transcriptional state that governs PRC2 binding, and we propose that it binds by default to nontranscribed CGI genes to maintain their silenced state and to protect cell identity.

U2 - 10.1016/j.molcel.2014.06.005

DO - 10.1016/j.molcel.2014.06.005

M3 - Journal article

C2 - 24999238

SN - 1097-2765

JO - Molecular Cell

JF - Molecular Cell

ER -