Dilution of contact frequency between superenhancers by loop extrusion at interfaces

Abstract

The loop extrusion theory predicts that cohesin acts as a molecular motor that extrudes chromatin fibers to produce loops. Hi-C experiments have detected relatively high contact frequencies between superenhancers. These probably result from the fact that superenhancers are localized at condensates of transcriptional activators and coactivators. The contact frequency between superenhancers is enhanced by auxin treatment that removes cohesin from chromatin. Motivated by these experimental results, we here treat chromatin at the surface of a condensate as a loop extruding polymer brush. Our theory predicts that the lateral pressure generated by the brush decreases with decreasing the loading rate of cohesin. This is because loop extrusion actively transfers chain segments at the vicinity of the interface. Our theory thus predicts that the increase of contact frequency by auxin treatment results from the fact that suppressing the loop extrusion process induces the dissolution of molecular components to the nucleoplasm, decreasing the average distance between superenhancers.