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Chemical-Induced Phase Transition and Global Conformational Reorganization of Chromatin [RNA-seq]

ABSTRACT: Chemicals or drugs were demonstrated to accumulate within biomolecule condensates formed through phase separation in cells. Here, we employed super-resolution imaging to search for chemicals that induce phase transition of chromatin at the microscale. We found that adriamycin (doxorubicin), a widely-used chemotherapeutic drug against malignancies, is able to induce local condensation and global conformational change of chromatin in cancer and primary cells. Hi-C and ATAC-seq experiments demonstrated 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 the phase transition of H1, forming fibrous aggregates in vitro. Our results reveal a new action mechanism of an anti-cancer drug discovered for decades, demonstrate the link between the physical properties of chromatin and gene expression, and suggest that interactions between drugs and biomolecules could exert profound effects on cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE222221 | GEO | 2023/01/11

REPOSITORIES: GEO

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