Chromatin organization by an interplay of loop extrusion and compartmental segregation

• DOI: 10.1073/pnas.1717730115
• Publication Date: 2018-07-02T19:18:09Z
• Authors: Johannes Nuebler; Geoffrey Fudenberg; Maxim Imakaev; Nezar Abdennur; Leonid A. Mirny
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; PNAS Plus; Chromosomal Proteins, Non-Histone; Animals; Cell Cycle Proteins; Chromatin Assembly and Disassembly; Chromosomes, Mammalian; Models, Biological; Cohesins; Chromatin

SignificanceHuman DNA is 2 m long and is folded into a 10-μm-sized cellular nucleus. Experiments have revealed two major features of genome organization: Segregation of alternating active and inactive regions into compartments, and formation of compacted local domains. These were hypothesized to be formed by different mechanisms: Compartments can be formed by microphase separation and domains by active, motor-driven, loop extrusion. Here, we integrate these mechanisms into a polymer model and show that their interplay coherently explains diverse experimental data for wild-type and mutant cells. Our results provide a framework for the interpretation of chromosome organization in cellular phenotypes and highlight that chromatin is a complex, active matter shaped by an interplay of phase segregation and loop extrusion.