Mechanism of loop-forming cohesin to suppress dynamic chromatin movement

Chromatin in eukaryotic nuclei forms locally compacted sub-megabase domains, but the mechanisms behind the formation of these domains are not yet fully understood. In this study, we investigate the dynamic behavior of chromatin to gain insights into this issue. Live-cell imaging of interphase human cells has demonstrated that cohesin-mediated loops constrain chromatin, thereby reducing the mean squared displacement (MSD) of chromatin movement. To explore whether different hypotheses for chromatin domain formation-such as the loop-extrusion and loop-capture models-can explain this observed reduction in MSD, we developed a polymer model of the chromatin chain. Our simulations highlight the importance of loop coverage and the complexity of loop topology in limiting chromatin movement. A version of the loop-extrusion model, which assumes a low extrusion rate in a cellular environment filled with obstacles that impede cohesin movement, predicts relatively high loop coverage and complexity. In contrast, in the loop-capture model, we examine a scenario where cohesin movement occurs solely through its association with actively transcribing RNA polymerase. However, this transcription-assisted sliding scenario in the loop-capture model results in low loop coverage, which does not align with the experimental data. While unresolved issues remain in both models, our simulation results indicate that understanding chromatin dynamics should provide a valuable framework for uncovering the mechanisms behind domain formation.