| Autor: |
Tengfei Wang, Shuxiang Shi, Yuanyuan Shi, Peipei Jiang, Ganlu Hu, Qinying Ye, Zhan Shi, Kexin Yu, Chenguang Wang, Guoping Fan, Suwen Zhao, Hanhui Ma, Alex C. Y. Chang, Zhi Li, Qian Bian, Chao-Po Lin |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-18 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-41340-4 |
| Popis: |
Abstract Chemicals or drugs can accumulate within biomolecular condensates formed through phase separation in cells. Here, we use super-resolution imaging to search for chemicals that induce phase transition within chromatin at the microscale. This microscopic screening approach reveals that adriamycin (doxorubicin) — a widely used anticancer drug that is known to interact with chromatin — specifically induces visible local condensation and global conformational change of chromatin in cancer and primary cells. Hi-C and ATAC-seq experiments systematically and quantitatively demonstrate that adriamycin-induced chromatin condensation is accompanied by weakened chromatin interaction within topologically associated domains, compartment A/B switching, lower chromatin accessibility, and corresponding transcriptomic changes. Mechanistically, adriamycin complexes with histone H1 and induces phase transition of H1, forming fibrous aggregates in vitro. These results reveal a phase separation-driven mechanism for a chemotherapeutic drug. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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