Time-dependent effect of 1,6-hexanediol on biomolecular condensates and 3D chromatin organization

• Published in: Genome Biology Vol. 22; no. 1; p. 230
• Main Authors: Liu, Xinyi, Jiang, Shaoshuai, Ma, Lin, Qu, Jiale, Zhao, Longying, Zhu, Xing, Ding, Junjun
• Format: Journal Article
• Language: English
• Published: England BioMed Central 17.08.2021; BMC
• Subjects: 1,6-Hexanediol; 3D chromatin organization; acute exposure; Apoptosis; Biomolecular condensates; Biomolecular Condensates - chemistry; Biomolecular Condensates - drug effects; Cell Physiological Phenomena; Cell viability; Chromatin; chronic exposure; Condensates; Gene loci; genome; Glycols - chemistry; Glycols - pharmacology; HeLa Cells; Humans; Imaging, Three-Dimensional; Phase transitions; Proteins; RNA polymerase; Stem cells; 1,6-Hexanediol; Biomolecular condensates; 3D chromatin organization
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-021-02455-3

Biomolecular condensates have been implicated in multiple cellular processes. However, the global role played by condensates in 3D chromatin organization remains unclear. At present, 1,6-hexanediol (1,6-HD) is the only available tool to globally disrupt condensates, yet the conditions of 1,6-HD vary considerably between studies and may even trigger apoptosis. In this study, we first analyzed the effects of different concentrations and treatment durations of 1,6-HD and found that short-term exposure to 1.5% 1,6-HD dissolved biomolecular condensates whereas long-term exposure caused aberrant aggregation without affecting cell viability. Based on this condition, we drew a time-resolved map of 3D chromatin organization and found that short-term treatment with 1.5% 1,6-HD resulted in reduced long-range interactions, strengthened compartmentalization, homogenized A-A interactions, B-to-A compartment switch and TAD reorganization, whereas longer exposure had the opposite effects. Furthermore, the long-range interactions between condensate-component-enriched regions were markedly weakened following 1,6-HD treatment. In conclusion, our study finds a proper 1,6-HD condition and provides a resource for exploring the role of biomolecular condensates in 3D chromatin organization.