Suppression of liquid–liquid phase separation by 1,6-hexanediol partially compromises the 3D genome organization in living cells

Ulianov, S.V.; Velichko, A.K.; Magnitov, M.D.; Luzhin, A.V.; Golov, A.K.; Ovsyannikova, N.; Kireev, I.I.; Gavrikov, A.S.; Mishin, A.S.; Garaev, A.K.; Tyakht, A.V.; Gavrilov, A.A.; Kantidze, O.L.; Razin, S.V.

Авторы: Ulianov Sergey V., Velichko Artem K., Magnitov Mikhail D., Luzhin Artem V., Golov Arkadiy K., Ovsyannikova Natalia, Kireev Igor I., Gavrikov Alexey S., Mishin Alexander S., Garaev Azat K., Tyakht Alexander V., Gavrilov Alexey A., Kantidze Omar L., Razin Sergey V.
Журнал: Nucleic Acids Research
Год издания: 2021
Издательство: Oxford University Press
Местоположение издательства: United Kingdom
DOI: 10.1093/nar/gkab249
Аннотация: Liquid–liquid phase separation (LLPS) contributes to the spatial and functional segregation of molecular processes within the cell nucleus. However, the roleplayed 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 distributionin 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 acquireinitial configurations, and resulted in more compact repressed chromatin than in untreated cells. 1,6-HDtreatment also weakened enhancer-promoter interactions and TAD insulation but did not considerably affect CTCF-dependent loops. Our results suggest that1,6-HD-sensitive LLPS plays a limited role in chromatin spatial organization by constraining its foldingpatterns and facilitating compartmentalization at different levels.
Добавил в систему: Киреев Игорь Игоревич

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Suppression of liquid–liquid phase separation by 1,6-hexanediol partially compromises the 3D genome organization in living cellsстатья

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