Enhancers regulate gene expression by forming contacts with distant promoters. Phase-separated condensates or clusters formed by transcription factors (TFs) and co-factors 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 multi-step 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.

4D Genome,enhancer-promoter contact,coarse-grained model