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PRC1凝聚体与SWI/SNF在染色质调控中的相互拮抗作用。

Mutual Antagonism Between PRC1 Condensates and SWI/SNF in Chromatin Regulation.

作者信息

Niekamp Stefan, Marr Sharon K, Sanon Rebecca, Schneider Philipp C, Subramanian Radhika, Kingston Robert E

机构信息

Department of Molecular Biology, Massachusetts General Hospital Research Institute, Massachusetts General Hospital, Boston, MA 02114, USA.

Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

出版信息

bioRxiv. 2025 Aug 26:2025.08.25.672128. doi: 10.1101/2025.08.25.672128.

Abstract

Opposing activities of conserved chromatin regulatory complexes, such as the Polycomb Repressive Complex 1 (PRC1) and the activating chromatin remodeler SWI/SNF play critical roles in regulating gene expression during development and differentiation. The mechanisms by which these complexes compete to regulate chromatin states remain poorly understood. We combine single-molecule analysis and genomic approaches in cultured cells to demonstrate that the condensate-forming properties of PRC1 play an important role in excluding SWI/SNF from chromatin. Consistently, PRC1 compositions with a higher propensity for condensate formation are more effective in preventing SWI/SNF binding. Conversely, SWI/SNF-bound chromatin significantly reduces PRC1 binding and subsequent condensate formation. Notably, SWI/SNF can suppress PRC1 condensate formation in an ATP-hydrolysis independent manner. We propose that the condensate properties of different PRC1 compositions drive mutual PRC1-SWI/SNF antagonism to properly balance these competing regulatory activities during development.

摘要

诸如多梳抑制复合物1(PRC1)和激活染色质重塑因子SWI/SNF等保守的染色质调控复合物的相反作用,在发育和分化过程中调节基因表达方面发挥着关键作用。这些复合物竞争调节染色质状态的机制仍知之甚少。我们在培养细胞中结合单分子分析和基因组方法,以证明PRC1的凝聚物形成特性在将SWI/SNF排除在染色质之外起着重要作用。一致地,具有更高凝聚物形成倾向的PRC1组成在防止SWI/SNF结合方面更有效。相反,与SWI/SNF结合的染色质显著降低PRC1结合及随后的凝聚物形成。值得注意的是,SWI/SNF可以以一种不依赖ATP水解的方式抑制PRC1凝聚物形成。我们提出,不同PRC1组成的凝聚物特性驱动PRC1与SWI/SNF之间的相互拮抗作用,以在发育过程中适当地平衡这些相互竞争的调控活动。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4135/12407733/43737ffce4e1/nihpp-2025.08.25.672128v1-f0001.jpg

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