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Wang, Tengfei; Shi, Shuxiang; Shi, Yuanyuan; Jiang, Peipei; Hu, Ganlu; Ye, Qinying; Shi, Zhan; Yu, Kexin; Wang, Chenguang; Fan, Guoping; Zhao, Suwen; Ma, Hanhui; Chang, Alex C. Y.; Li, Zhi; Bian, Qian; Lin, Chao-Po
Nature communications, 09/2023, Letnik: 14, Številka: 1Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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