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| Status |
Public on Jun 14, 2022 |
| Title |
Reorganization of 3D chromatin architecture in doxorubicin-resistant breast cancer cells |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Doxorubicin resistance remains a major therapeutic challenge leading to treatment failure and poor survival prognosis in breast cancer. Although doxorubicin induces massive changes in the transcriptional landscape accompanied by alterations of chromatin accessibility are well known, potential diagnostic or therapeutic targets associated with three-dimensional (3D) genome reorganization in doxorubicin-resistant breast cancer cells have not yet been systematically investigated. Here we performed integrated analyses combining in situ high-throughput chromosome conformation capture (Hi-C), ATAC-seq and mHi-C data on doxorubicin-resistant MCF7 human breast cancer cells compared to parental cells. It revealed that A/B compartment switching was positively correlated to genome-wide differential gene expression, and the genome was spatially reorganized into smaller topologically associating domains (TADs) and loops. We also revealed the contribution of increased chromatin accessibility and potential transcription factor families, including CTCF and BORIS, to gained TAD boundaries and loop anchors. Intriguingly, we observed two condensed genomic regions (~20kb) with decreased chromatin accessibility flanking TAD boundaries, which might play a critical role in the formation or maintenance of TADs. Moreover, we identified a number of gained and lost enhancer-promoter interactions associated with differentially expressed genes, including FA2H, FOXA1, JRKL and EZH, some of which involved in chromatin organization and breast cancer signaling pathways. This study uncovered a close connection between 3D genome reorganization, chromatin accessibility as well as gene transcription, and provides resources and novel insights into the epigenomic mechanisms with potential therapeutic implications for doxorubicin resistance in breast cancer.
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| Overall design |
Genome-wide landscaps of 3D chromatin architecture in parental and doxorubicin-resistant breast cancer cells. In total, 4 samples were analyzed. Hi-C_MCF7_1 and Hi-C_MCF7_2 were two biological replicates and served as the control group. Hi-C_MCF7-DR_1 and Hi-C_MCF7-DR_2 were two biological replicates and served as the treatment group.
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| Contributor(s) |
Wang X |
| Citation(s) |
36003143 |
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| Submission date |
Jun 10, 2022 |
| Last update date |
Aug 31, 2022 |
| Contact name |
Xuelong Wang |
| E-mail(s) |
wangxuelong100@126.com
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| Organization name |
Chinese Academy of Sciences
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| Street address |
No. 320 Yueyang Road
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| City |
Shanghai |
| ZIP/Postal code |
200031 |
| Country |
China |
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| Platforms (1) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA847983 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE205874_Hi-C_library_sequencing_statistics.xlsx |
28.2 Kb |
(ftp)(http) |
XLSX |
| GSE205874_Identified_chromatin_loops.xlsx |
642.1 Kb |
(ftp)(http) |
XLSX |
| GSE205874_Identified_topologically_associating_domains.xlsx |
647.8 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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