Journal
NUCLEIC ACIDS RESEARCH
Volume 49, Issue 18, Pages 10524-10541Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab249
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Funding
- Russian Science Foundation [19-74-10009]
- Ministry of Science and Higher Education of the Russian Federation [07515-2019-1661]
- Russian Science Foundation [19-74-10009] Funding Source: Russian Science Foundation
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The study found that treatment with 1,6-hexanediol caused changes in chromatin topology, resulting in the mixing of chromatin compartments. Moreover, removing 1,6-hexanediol from the culture medium did not allow chromatin to return to its initial structure, leading to a more compact chromatin compared to untreated cells.
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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