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| Status |
Public on Dec 11, 2019 |
| Title |
Deregulation of the three-dimensional epigenome in endocrine resistant breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Around 35% of Estrogen Receptor (ER) positive patients develop resistance and relapse, highlighting the need to further understand the mechanisms underpinning endocrine resistance in breast cancer. Here, we study 3-dimensional (3D) epigenome remodelling in endocrine resistant breast cancer cells. We show that chromatin interactions both within and between topologically associating domains (TADs) frequently change in resistant breast cancer cells and that alterations in active (A-type) and inactive (B-type) chromosomal compartments are associated with decreased ER binding and atypical interactions and gene expression. Finally, we identify differentially interacting ER-bound regions that preferentially connect active enhancers and promoters associated with altered expression of ER-regulated genes. Importantly, interactions specifically associated with endocrine resistance, often occur coincidently with hypermethylation of ER binding. Our results demonstrate that 3D epigenome remodelling is a key mechanism of endocrine resistance that consists of differential chromatin interactions and aberrant DNA methylation at ER-regulated enhancer regions.
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| Overall design |
Hi-C was conducted in endocrine-sensitive breast cancer cells (MCF7) at three time-points during long-term culture: time zero (T0), time point mid and late time point (> 6 months)
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| Contributor(s) |
Achinger-Kawecka J |
| Citation(s) |
31949157 |
| |
| Submission date |
May 08, 2019 |
| Last update date |
Jan 19, 2020 |
| Contact name |
Joanna Achinger-Kawecka |
| E-mail(s) |
joanna.achinger@adelaide.edu.au
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| Organization name |
South Australian Immunogenomics Cancer Institute
|
| Street address |
AHMS Building, North Terrace
|
| City |
Adelaide |
| State/province |
SA |
| ZIP/Postal code |
5005 |
| Country |
Australia |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA541942 |
| SRA |
SRP197114 |
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