Fluctuating chromatin facilitates enhancer-promoter communication by regulating transcriptional clustering dynamics

AbstractEnhancers 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. Graphical TOC Entry O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/610578v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@114b51borg.highwire.dtl.DTLVardef@7e261forg.highwire.dtl.DTLVardef@1f8dc3forg.highwire.dtl.DTLVardef@143ecb5_HPS_FORMAT_FIGEXP M_FIG C_FIG