Genome folding by cohesion.

Abstract

Chromosomes in eukaryotic cells undergo compaction at multiple levels and are folded into hierarchical structures to fit into the nucleus with limited dimensions. Three-dimensional genome organization needs to be coordinated with chromosome-templated processes, including DNA replication and gene transcription. As an ATPase molecular machine, the cohesin complex is a major driver of genome folding, which regulates transcription by modulating promoter-enhancer contacts. Here, we review our current understanding of genome folding by cohesin. We summarize the available evidence supporting a role of loop extrusion by cohesin in forming chromatin loops and topologically associating domains. We describe different conformations of cohesin and discuss the regulation of loop extrusion by cohesin-binding factors and loop-extrusion barriers. Finally, we propose a dimeric inchworm model for cohesin-mediated loop extrusion.