Chromatin organization by an interplay of loop extrusion and compartmental segregation

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
DOI: 10.1073/pnas.1717730115 Publication Date: 2018-07-02T19:18:09Z
ABSTRACT
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.
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