PRC1 的模块化组成和染色质相互作用决定了凝聚态的特性。

IF 14.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Cell Pub Date : 2024-05-02 Epub 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
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引用次数: 0

摘要

多角体抑制复合体(PRCs)在基因抑制中发挥着关键作用,是正常发育不可或缺的因素。典型的 PRC1 在体外和细胞内形成凝聚体,被认为有助于抑制的维持。然而,染色质和 PRC1 的各种亚基是如何促成凝集的在很大程度上还没有被研究。我们利用重组方法和单分子成像技术证明,核糖体阵列和 PRC1 具有协同作用,可将凝集所需的临界浓度降低 20 倍以上。我们发现,PHC 和 CBX 亚基的确切组合决定了凝聚体的启动、形态、稳定性和动力学。特别是,PHC2 的聚合活性通过促进形成相互粘附但不凝聚的不同结构域来影响凝聚态的动力学。活细胞成像证实了 CBX 在凝集物启动过程中的作用,并强调了 PHC 对凝集物稳定性的重要性。我们提出,PRC1 的组成可以调节凝聚态的特性,从而在不同发育阶段提供至关重要的调控灵活性。
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Modularity of PRC1 composition and chromatin interaction define condensate properties.

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.

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来源期刊
Molecular Cell
Molecular Cell 生物-生化与分子生物学
CiteScore
26.00
自引率
3.80%
发文量
389
审稿时长
1 months
期刊介绍: Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly. Molecular Cell is dedicated to publishing cutting-edge research in molecular biology, focusing on fundamental cellular processes. The journal encompasses a wide range of topics, including DNA replication, recombination, and repair; Chromatin biology and genome organization; Transcription; RNA processing and decay; Non-coding RNA function; Translation; Protein folding, modification, and quality control; Signal transduction pathways; Cell cycle and checkpoints; Cell death; Autophagy; Metabolism.
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