Fluctuating\nChromatin Facilitates Enhancer–Promoter\nCommunication by Regulating Transcriptional Clustering Dynamics

Enhancers\nregulate gene expression by forming contacts with distant\npromoters. Phase-separated condensates or clusters formed by transcription\nfactors (TFs) and cofactors are thought to facilitate these enhancer–promoter\n(E–P) interactions. Using polymer physics, we developed distinct\ncoarse-grained chromatin models that produce similar ensemble-averaged\nHi-C maps but with “stable” and “dynamic”\ncharacteristics. Our findings, consistent with recent experiments,\nreveal a multistep E–P communication process. The dynamic model\nfacilitates E–P proximity by enhancing TF clustering and subsequently\npromotes direct E–P interactions by destabilizing the TF clusters\nthrough chain flexibility. Our study promotes physical understanding\nof the molecular mechanisms governing E–P communication in\ntranscriptional regulation.