Human cohesin compacts DNA by loop extrusion

TLDR

Cohesin is a chromosome‑bound, multisubunit ATPase complex that, after loading onto chromosomes, generates loops to regulate chromosome functions, and although loop extrusion has been proposed as a mechanism for genome organization, direct evidence has been lacking. The study uses single‑molecule imaging to demonstrate that recombinant human cohesin‑NIPBL compacts both naked and nucleosome‑bound DNA by extruding loops. Using single‑molecule imaging, the authors show that cohesin compacts DNA via ATP‑dependent, force‑sensitive loop extrusion. The process is processive over tens of kilobases at ~0.5 kb/s, operates bidirectionally as suggested by double‑tethered DNA experiments, and establishes cohesin‑NIPBL as an ATP‑driven molecular machine capable of loop extrusion.

Abstract

Cohesin is a chromosome-bound, multisubunit adenosine triphosphatase complex. After loading onto chromosomes, it generates loops to regulate chromosome functions. It has been suggested that cohesin organizes the genome through loop extrusion, but direct evidence is lacking. Here, we used single-molecule imaging to show that the recombinant human cohesin-NIPBL complex compacts both naked and nucleosome-bound DNA by extruding DNA loops. DNA compaction by cohesin requires adenosine triphosphate (ATP) hydrolysis and is force sensitive. This compaction is processive over tens of kilobases at an average rate of 0.5 kilobases per second. Compaction of double-tethered DNA suggests that a cohesin dimer extrudes DNA loops bidirectionally. Our results establish cohesin-NIPBL as an ATP-driven molecular machine capable of loop extrusion.