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Identification of regulators of the three-dimensional polycomb organization by a microscopy-based genome-wide RNAi screen

机译：通过基于显微镜的全基因组RNAi筛选鉴定三维多梳组织的调节因子

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Polycomb group (PcG) proteins dynamically define cellular identities through epigenetic repression of key developmental genes. PcG target gene repression can be stabilized through the interaction in the nucleus at PcG foci. Here, we report the results of ahigh-resolution microscopy genome-wide RNAi screen that identifies 129 genes that regulate the nuclear organization of Pc foci. Candidate genes include PcG components and chromatin factors, as well as many protein-modifying enzymes, including components of the SUMOylation pathway. In the absence of SUMO, Pc foci coagulate into larger aggregates. Conversely, loss of function of the SUMO peptidase Velo disperses Pc foci. Moreover, SUMO and Velo colocalize with PcG proteins at PREs, and Pc SUMOylation affects its chromatin targeting, suggesting that the dynamic regulation of Pc SUMOylation regulates PcG-mediated silencing by modulating the kinetics of Pc binding to chromatin as well as its ability to form Polycomb foci.
机译：Polycomb group（PcG）蛋白通过关键发育基因的表观遗传抑制来动态定义细胞身份。 PcG靶基因的阻遏可以通过PcG病灶中细胞核中的相互作用来稳定。在这里，我们报告高分辨率显微术全基因组RNAi筛选的结果，该筛选可识别129个调控Pc灶核组织的基因。候选基因包括PcG成分和染色质因子，以及许多蛋白质修饰酶，包括SUMOylation途径的成分。在没有SUMO的情况下，Pc病灶会凝结成更大的聚集体。相反，SUMO肽酶Velo功能的丧失分散了Pc病灶。此外，SUMO和Velo在PRE处与PcG蛋白共定位，并且Pc SUMOylation影响其染色质靶向，这表明Pc SUMOylation的动态调节通过调节Pc与染色质结合的动力学及其形成Polycomb的能力来调节PcG介导的沉默。焦点。

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