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Modularity of PRC1 composition and chromatin interaction define condensate properties
Molecular Cell ( IF 16.0 ) Pub Date : 2024-03-22 , DOI: 10.1016/j.molcel.2024.03.001
Stefan Niekamp , Sharon K. Marr , Theresa A. Oei , Radhika Subramanian , Robert E. Kingston

Polycomb repressive complexes (PRCs) play a key role in gene repression and are indispensable for proper development. Canonical PRC1 forms condensates in vitro and in cells that are proposed to contribute to the maintenance of repression. However, how chromatin and the various subunits of PRC1 contribute to condensation is largely unexplored. Using a reconstitution approach and single-molecule imaging, we demonstrate that nucleosomal arrays and PRC1 act synergistically, reducing the critical concentration required for condensation by more than 20-fold. We find that the exact combination of PHC and CBX subunits determines condensate initiation, morphology, stability, and dynamics. Particularly, PHC2’s polymerization activity influences condensate dynamics by promoting the formation of distinct domains that adhere to each other but do not coalesce. Live-cell imaging confirms CBX’s role in condensate initiation and highlights PHC’s importance for condensate stability. We propose that PRC1 composition can modulate condensate properties, providing crucial regulatory flexibility across developmental stages.



中文翻译:

PRC1 组成的模块化和染色质相互作用定义了凝聚物的特性

多梳抑制复合物(PRC)在基因抑制中发挥着关键作用,对于正常发育是不可或缺的。 Canonical PRC1在体外和细胞内形成凝聚物,有助于维持抑制。然而,染色质和 PRC1 的各个亚基如何促进凝聚在很大程度上尚未被探索。使用重构方法和单分子成像,我们证明了核小体阵列和 PRC1 协同作用,将浓缩所需的临界浓度降低了 20 倍以上。我们发现 PHC 和 CBX 亚基的精确组合决定了冷凝物的引发、形态、稳定性和动力学。特别是,PHC2 的聚合活性通过促进相互粘附但不聚结的不同域的形成来影响凝聚动力学。活细胞成像证实了 CBX 在凝析油引发中的作用,并强调了 PHC 对凝析油稳定性的重要性。我们认为 PRC1 成分可以调节凝析油特性,从而在整个发展阶段提供至关重要的监管灵活性。

更新日期:2024-03-22
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