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Series GSE118711 Query DataSets for GSE118711
Status Public on Dec 11, 2019
Title Epigenetic reprogramming at estrogen-receptor binding sites alters the 3D chromatin landscape in endocrine resistant breast cancer [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
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.
 
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.
 
Contributor(s) Achinger-Kawecka J
Citation(s) 31949157
Submission date Aug 17, 2018
Last update date Jan 19, 2020
Contact name Joanna Achinger-Kawecka
E-mail(s) j.achinger@garvan.org.au
Organization name Garvan Institute of Medical Research
Street address 384 Victoria Street
City Darlinghurst
State/province NSW
ZIP/Postal code 2010
Country Australia
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (14)
GSM3336876 MCF7_H2AZac_ChIP-seq
GSM3336877 TAMR_H2AZac_ChIP-seq
GSM3336878 FASR_H2AZac_ChIP-seq
This SubSeries is part of SuperSeries:
GSE118716 Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine resistant breast cancer
Relations
BioProject PRJNA486527
SRA SRP158275

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Supplementary file Size Download File type/resource
GSE118711_RAW.tar 13.9 Mb (http)(custom) TAR (of BB)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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