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| Status |
Public on Dec 11, 2019 |
| Title |
Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [WGBS] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Endocrine therapy resistance invariably develops in estrogen receptor positive (ER+) breast cancer, but the underlying molecular mechanisms are largely unknown. Here, we show that 3-dimensional (3D) chromatin interactions both within and between topologically associating domains (TADs) frequently change in ER+ endocrine resistant breast cancer cells and that the differential interactions are enriched for genetic variants at CTCF-bound anchors. Ectopic chromatin interactions are preferentially enriched at active enhancers and promoters and ER binding sites and are associated with altered expression of ER-regulated genes, consistent with dynamic remodelling of ER pathways accompanying the development of endocrine resistance. Importantly, new 3D chromatin interactions often occur coincidently with hypermethylation and loss of ER binding. Additionally, alterations in active (A-type) and inactive (B-type) chromosomal compartments are also associated with decreased ER binding and atypical interactions and gene expression. Together, our results suggest that 3D epigenome remodelling is a key mechanism underlying endocrine resistance in ER+ breast cancer.
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| Overall design |
Hi-C, WGS, WGBS, ChIP-seq and RNA-seq were conducted in endocrine-sensitive breast cancer cells (MCF7) and its two endocrine-resistant derivatives - tamoxifen-resistant (TAMR) cells and fulvestrant-resistant (FASR) cells.
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| Contributor(s) |
Achinger-Kawecka J |
| Citation(s) |
31949157, 38448820 |
| Submission date |
Aug 17, 2018 |
| Last update date |
Mar 13, 2024 |
| Contact name |
Joanna Achinger-Kawecka |
| E-mail(s) |
j.achinger@garvan.org.au
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| Organization name |
Garvan Institute of Medical Research
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| Lab |
Epigenetics Research Laboratory
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| Street address |
384 Victoria Street
|
| City |
Darlinghurst |
| State/province |
NSW |
| ZIP/Postal code |
2010 |
| Country |
Australia |
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| Platforms (1) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE118716 |
Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine resistant breast cancer |
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| Relations |
| BioProject |
PRJNA486530 |
| SRA |
SRP158279 |
