Overlap reduction, entanglement dilution, and anomalous dynamics of active polymer melts regulated by active loop extrusion

Long chains in passive polymer melts are topologically restricted by many overlapping neighboring chains. Despite their long contour lengths, experiments suggest that mammalian chromosomes do not interpenetrate significantly, and sections of chromatin called topologically associated domains (TADs) tend to be spatially segregated. We predicted that activity in the form of active loop extrusion prevents complete relaxation of TADs causing chromatin compaction and entanglement dilution. Here, we model active loop extrusion with coarse-grained molecular dynamics simulations of active polymer melts. Polymers with active loop extrusion are smaller in size than their equilibrium counterparts. As such, overlaps between neighboring polymer sections are reduced. The overlap parameter of TADs is on the order of unity, meaning that contacts within TADs are enhanced. Furthermore, active loop extrusion strongly suppresses entanglements within the scales of our simulations. We also show that active loop extrusion causes anomalous dynamics not only on the single locus (monomeric) level, but also on larger scales. In particular, we predict the mean square displacement of individual loci to exhibit a regime that scales with the one-third power of time. This work suggests that active loop extrusion reduces overlaps between TADs, contributing to effective gene regulation by cis-regulatory elements.