Enhancers regulate gene expression by forming contacts with distant promoters. Phase-separated condensates or clusters formed by transcription factors (TFs) and cofactors are thought to facilitate these enhancer–promoter (E–P) interactions. Using polymer physics, we developed distinct coarse-grained chromatin models that produce similar ensemble-averaged Hi-C maps but with “stable” and “dynamic” characteristics. Our findings, consistent with recent experiments, reveal a multistep E–P communication process. The dynamic model facilitates E–P proximity by enhancing TF clustering and subsequently promotes direct E–P interactions by destabilizing the TF clusters through chain flexibility. Our study promotes physical understanding of the molecular mechanisms governing E–P communication in transcriptional regulation.

中文翻译：

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波动的染色质通过调节转录聚集动力学促进增强子-启动子通讯


增强子通过与远处启动子形成接触来调节基因表达。由转录因子 （TFs） 和辅因子形成的相分离凝聚物或簇被认为促进了这些增强子-启动子 （E-P） 相互作用。利用聚合物物理学，我们开发了独特的粗粒染色质模型，这些模型产生了类似的集成平均 Hi-C 图，但具有“稳定”和“动态”特性。我们的研究结果与最近的实验一致，揭示了一个多步骤的 E-P 通信过程。动态模型通过增强 TF 聚类来促进 E-P 接近，随后通过链灵活性破坏 TF 簇的稳定性来促进直接的 E-P 相互作用。我们的研究促进了对转录调控中控制 E-P 通讯的分子机制的物理理解。