Niekamp Stefan, Marr Sharon K, Sanon Rebecca, Schneider Philipp C, Subramanian Radhika, Kingston Robert E
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.
bioRxiv. 2025 Aug 26:2025.08.25.672128. doi: 10.1101/2025.08.25.672128.
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.
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。
