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
AUTHORS (5)
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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