Suppression of Liquid-liquid Phase Separation by 1,6-hexanediol Partially Compromises the 3D Genome Organization in Living Cells

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2021 Apr 9

PMID 33836078

Citations 51

Authors

Sergey V Ulianov

Artem K Velichko

Mikhail D Magnitov

Artem V Luzhin

Arkadiy K Golov

Natalia Ovsyannikova

Igor I Kireev

Alexey S Gavrikov

Alexander S Mishin

Azat K Garaev

Alexander V Tyakht

Alexey A Gavrilov

Omar L Kantidze

Sergey V Razin

Affiliations

Soon will be listed here.

Abstract

Liquid-liquid phase separation (LLPS) contributes to the spatial and functional segregation of molecular processes within the cell nucleus. However, the role played by LLPS in chromatin folding in living cells remains unclear. Here, using stochastic optical reconstruction microscopy (STORM) and Hi-C techniques, we studied the effects of 1,6-hexanediol (1,6-HD)-mediated LLPS disruption/modulation on higher-order chromatin organization in living cells. We found that 1,6-HD treatment caused the enlargement of nucleosome clutches and their more uniform distribution in the nuclear space. At a megabase-scale, chromatin underwent moderate but irreversible perturbations that resulted in the partial mixing of A and B compartments. The removal of 1,6-HD from the culture medium did not allow chromatin to acquire initial configurations, and resulted in more compact repressed chromatin than in untreated cells. 1,6-HD treatment also weakened enhancer-promoter interactions and TAD insulation but did not considerably affect CTCF-dependent loops. Our results suggest that 1,6-HD-sensitive LLPS plays a limited role in chromatin spatial organization by constraining its folding patterns and facilitating compartmentalization at different levels.

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