Cohesin and condensin extrude loops in a cell-cycle dependent manner

Abstract

AbstractChromatin undergoes a dramatic reorganization during the cell cycle1–3. In interphase, chromatin is organized into compartments and topological-associating domains (TADs) that are cell-type specific4–7, whereas in metaphase, chromosomes undergo large-scale compaction, leading to the loss of specific boundaries and the shutdown of transcription8–12. Loop extrusion by structural maintenance of chromosomes complexes (SMCs) has been proposed as a mechanism to organize chromatin in interphase and metaphase13–19. However, the requirements for chromatin organization in these cell phases are very different, and it is unknown whether loop extrusion dynamics and the complexes that extrude them also differ. Here, we used Xenopus egg extracts to reconstitute and image loop extrusion of single DNA molecules during the cell cycle. We show that loops form in both metaphase and interphase, but with distinct dynamic properties. Condensin extrudes asymmetric loops in metaphase, whereas cohesin extrudes symmetric loops in interphase. Our data show that loop extrusion is a general mechanism for the organization of DNA, with dynamic and structural properties that are molecularly regulated during the cell cycle.