Non-core Subunits of the PRC2 Complex Are Collectively Required for Its Target-Site Specificity
Non-core Subunits of the PRC2 Complex Are Collectively Required for Its Target-Site Specificity
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DOI：
10.1016/j.molcel.2019.07.031
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发表时间：
2019-11-07
期刊：
影响因子：
16
通讯作者：
Helin, Kristian
中科院分区：
文献类型：
--
作者：
Hojfeldt, Jonas Westergaard;Hedehus, Lin;Helin, Kristian
Polycomb抑制复合体2 （PRC2）催化整个基因组的H3K27甲基化，影响转录调控，对建立细胞身份至关重要。由于其在发育和癌症中的重要功能，了解全基因组H3K27甲基化模式的描述一直是激烈研究的焦点。PRC2甲基化活性丰富且分散在整个基因组中，但最高活性专门针对H3K27me3高度富集的稳定占据的靶点子集。在这里，我们通过系统地敲除小鼠胚胎干细胞中PRC2复合体的单个和多个非核心亚基，表明它们每个都有助于将PRC2活性导向目标位点。此外，6个非核心亚基的联合敲除表明，尽管H3K27的整体甲基化水平是不需要的，但非核心PRC2亚基对于将H3K27me3活性集中到基因组中的特定位点是必需的。
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.