When motors collide: how transcription and loop-extruding cohesins organize chromatin

The SMC complex cohesin organizes interphase chromatin into loops by a process known as "loop extrusion," through which cohesin progressively reels in DNA and extrudes it as a loop. Extrusion can generate distinctive patterns in genomic spatial organization through interactions with stationary "boundary elements," such as CTCF proteins. Less is known about whether and how extrusion is impeded by other elements on the molecularly crowded genome, such as translocating RNA polymerase motors. We analyze chromosome conformation capture (Hi-C) data near active genes, including in conditions in which cohesin dynamics or transcription are perturbed. We develop a model in which RNA polymerases act as "moving barriers,"  impeding and pushing translocating cohesins as they continue to extrude loops. Simulations of the model reproduce experimentally observed cohesin accumulation and genomic contact patterns. We develop a theory that explains how cohesin accumulation patterns result from the probability of encounter with polymerase and cohesin lifetimes on chromatin. Our analysis thus demonstrates how transcriptional activity shapes the genome by modulating the activity of loop-extruding cohesin motors.