Journal
GENOME BIOLOGY
Volume 22, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13059-021-02455-3
Keywords
1; 6-Hexanediol; Biomolecular condensates; 3D chromatin organization
Funding
- National Key Research and Development Program of China Stem Cell and Translational Research [2017YFA0102800, 2016YFA 0101700]
- National Natural Science Foundation of China [31970811, 31771639]
- Frontier Research Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) [2018GZR110105007]
- Guangdong Innovative and Entrepreneurial Research Team Program [2016ZT06S029]
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Our study identified a proper condition of 1,6-HD for disrupting biomolecular condensates and provided insights into the role of condensates in 3D chromatin organization. Short-term exposure to 1.5% 1,6-HD resulted in specific changes in chromatin organization, while longer exposure had contrasting effects.
Background 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. Results 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. Conclusions 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.
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