Chromosome biology: How to build a cohesive genome in 3D.

Abstract

Removing the protein complex cohesin from chromosomes destroys one layer of the genome's 3D structure but leaves another intact. Genome structure is therefore built by independent processes that work together. See Letter p.51 The nuclear organization of interphase chromosomes is thought to be mediated by architectural protein complexes such as CTCF and cohesin, which are found at loops and at the boundaries of topological domains (TADs). However, experimental depletion of these proteins has shown limited impact on chromosome organization. Here, Francois Spitz and colleagues perform an inducible deletion of the cohesin-loading factor Nipbl in liver cells in mice. They find that depletion of chromosome-associated cohesin leads to the loss of TADs and TAD-associated loops, but segregation of the genome into compartments is preserved and transcription is affected only at a subset of genes. The disappearance of TADs unmasks a finer compartment structure that reflects local transcriptional activity. Genome organization therefore seems to result from two distinct mechanisms with different requirements for cohesin.