Criticality-driven enhancer-promoter dynamics in Drosophila chromosomes

Recent live imaging in Drosophila embryonic nuclei revealed frequent enhancer–promoter (E–P) contacts across megabase-scale distances, challenging classical polymer models. To identify the physical mechanisms enabling such long-range communication, we performed coarse-grained polymer simulations exploring three chromatin organization modes: ideal polymers, loop extrusion, and compartmental segregation. We found that compartmental segregation, when tuned near the coil–globule phase transition, best captured the experimentally observed structure and dynamics. Adding loop extrusion further improved the agreement with experimental data, suggesting a synergistic interplay. These results indicate that Drosophila chromatin folds near a critical point, enabling dynamic E–P interactions over long distances. Our findings provide a mechanistic framework for chromatin architecture during development and point to criticality as a potentially universal principle of genome organization.