Universal dynamics of cohesin-mediated loop extrusion

Most animal genomes are partitioned into Topologically Associating Domains (TADs), created by cohesin-mediated loop extrusion and defined by convergently oriented CTCF sites. The dynamics of loop extrusion and its regulation remains poorly characterized in vivo. Here, we tracked TAD anchors in living human cells to visualize and quantify cohesin-dependent loop extrusion across multiple endogenous genomic regions. We show that TADs are dynamic structures whose anchors are brought in proximity about once per hour and for 6-19 min (~16% of the time). TADs are continuously subjected to extrusion by multiple cohesin complexes, extruding loops at ~0.1 kb/s. Remarkably, despite strong differences of Hi-C patterns between the chromatin regions, their dynamics is consistent with the same density, residence time and speed of cohesin. Our results suggest that TAD dynamics is governed primarily by CTCF site location and affinity, which allows genome-wide predictive models of cohesin-dependent interactions. We performed Capture Micro-C in HCT116 cells treated or not with 500 𝞵M auxin (leading to RAD21 depletion) for 3 hours. We used cell lines with TetO and CuO repeats inserted in the genome at the L1, L2, T1 and No Loop genomic regions.