Suppression of liquid–liquid phase separation by 1,6-hexanediol partially compromises the 3D genome organization in living cells
Autor: | Azat K. Garaev, Mikhail D. Magnitov, Sergey V. Ulianov, Natalia Ovsyannikova, Alexander S. Mishin, Igor I. Kireev, Omar L. Kantidze, Alexander V. Tyakht, Sergey V. Razin, Artem V. Luzhin, Alexey A. Gavrilov, Alexey S. Gavrikov, Arkadiy K. Golov, Artem K. Velichko |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
AcademicSubjects/SCI00010
Biology 03 medical and health sciences Glycols 0302 clinical medicine Genetics medicine Nucleosome Liquid liquid Humans Promoter Regions Genetic 030304 developmental biology Genomic organization 0303 health sciences Microscopy Genome Human Genomics Compartmentalization (psychology) Optical reconstruction Chromatin Folding (chemistry) Cell nucleus medicine.anatomical_structure Enhancer Elements Genetic Biophysics 030217 neurology & neurosurgery HeLa Cells |
Zdroj: | Nucleic Acids Research |
ISSN: | 1362-4962 0305-1048 |
Popis: | 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. |
Databáze: | OpenAIRE |
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