TY - JOUR
T1 - Non-core Subunits of the PRC2 Complex Are Collectively Required for Its Target-Site Specificity
AU - Højfeldt, Jonas Westergaard
AU - Hedehus, Lin
AU - Laugesen, Anne
AU - Tatar, Tülin
AU - Wiehle, Laura
AU - Helin, Kristian
N1 - Copyright © 2019 Elsevier Inc. All rights reserved.
PY - 2019/11/7
Y1 - 2019/11/7
N2 - The Polycomb repressive complex 2 (PRC2) catalyzes H3K27 methylation across the genome, which impacts transcriptional regulation and is critical for establishment of cell identity. Because of its essential function during development and in cancer, understanding the delineation of genome-wide H3K27 methylation patterns has been the focus of intense investigation. PRC2 methylation activity is abundant and dispersed throughout the genome, but the highest activity is specifically directed to a subset of target sites that are stably occupied by the complex and highly enriched for H3K27me3. Here, we show, by systematically knocking out single and multiple non-core subunits of the PRC2 complex in mouse embryonic stem cells, that they each contribute to directing PRC2 activity to target sites. Furthermore, combined knockout of six non-core subunits reveals that, while dispensable for global H3K27 methylation levels, the non-core PRC2 subunits are collectively required for focusing H3K27me3 activity to specific sites in the genome.
AB - The Polycomb repressive complex 2 (PRC2) catalyzes H3K27 methylation across the genome, which impacts transcriptional regulation and is critical for establishment of cell identity. Because of its essential function during development and in cancer, understanding the delineation of genome-wide H3K27 methylation patterns has been the focus of intense investigation. PRC2 methylation activity is abundant and dispersed throughout the genome, but the highest activity is specifically directed to a subset of target sites that are stably occupied by the complex and highly enriched for H3K27me3. Here, we show, by systematically knocking out single and multiple non-core subunits of the PRC2 complex in mouse embryonic stem cells, that they each contribute to directing PRC2 activity to target sites. Furthermore, combined knockout of six non-core subunits reveals that, while dispensable for global H3K27 methylation levels, the non-core PRC2 subunits are collectively required for focusing H3K27me3 activity to specific sites in the genome.
U2 - 10.1016/j.molcel.2019.07.031
DO - 10.1016/j.molcel.2019.07.031
M3 - Journal article
C2 - 31521506
SN - 1097-2765
VL - 76
SP - 423
EP - 436
JO - Molecular Cell
JF - Molecular Cell
IS - 3
M1 - E3
ER -
