EXPERIMENT_TITLE: GSM8490549: ANTH_K562_HiC_dauno_rep2; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Cells were crosslinked with 1% formaldehyde for 10 min, quenched with 2.0M glycine for 5 min, washed in PBS, and split into 3x106 cell pellet aliquots in situ Hi-C
STUDY_DESCRIPTOR_STUDY_ABSTRACT: The chromatins are folded into three-dimensional (3D) structures inside cells, which coordinates the regulation of gene transcription by the non-coding regulatory elements. Aberrant chromatin 3D folding has been shown in many diseases, such as acute myeloid leukemia (AML), and may contribute to tumorigenesis. The anthracycline topoisomerase II inhibitors can induce histone eviction and DNA damage. We performed genome-wide high-resolution mapping of the chemotherapeutic effects of various clinically used anthracycline drugs. ATAC-seq was used to profile the histone eviction effects of different anthracyclines. TOP2A ChIP-seq was used to profile the potential DNA damage regions. Integrated analyses show that different anthracyclines have distinct target selectivity on epigenomic regions, based on their respective ATAC-seq and ChIP-seq profiles. We identified the underlying molecular mechanism that unique anthracycline variants selectively target chromatin looping anchors via disrupting CTCF binding, suggesting an additional potential therapeutic effect on the 3D genome. We further performed Hi-C experiments, and data from K562 cells treated with the selective anthracycline drugs indicate that the 3D chromatin organization is disrupted. Furthermore, AML patients receiving anthracycline drugs showed altered chromatin structures around potential looping anchors of, which linked to distinct clinical outcomes. Our data indicate that anthracyclines are potent and selective epigenomic targeting drugs and can target the 3D genome for anticancer therapy, which could be used for personalized medicine to treat tumors with aberrant 3D chromatin structures Overall design: Hi-C of K562 cells treated with DMSO, daunorubicin, or aclarubicin for 2h.
SAMPLE_TITLE: ANTH_K562_HiC_dauno_rep2
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "K562"}, {"TAG": "cell line", "VALUE": "K562"}, {"TAG": "cell type", "VALUE": "Human leukemia"}, {"TAG": "genotype", "VALUE": "WT"}, {"TAG": "treatment", "VALUE": "daunorubicin"}, {"TAG": "geo_loc_name", "VALUE": "missing"}, {"TAG": "collection_date", "VALUE": "missing"}]
Pool_Member_@attributes_sample_title: ANTH_K562_HiC_dauno_rep2
RUN_SET_RUN_Pool_Member_@attributes_sample_title: ANTH_K562_HiC_dauno_rep2
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