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Series GSE171066 Query DataSets for GSE171066
Status Public on Dec 12, 2021
Title Epigenetic therapy suppresses tumour growth by rewiring ER-mediated long-range chromatin interactions in ER+ endocrine-resistant breast cancer [methylation GAR15-13]
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary Here we investigate the impact of epigenetic therapy with Decitabine in endocrine-resistant ER+ breast cancer by using patient-derived xenograft (PDX) models. Decitabine treatment restrained tumour growth, inhibited cell proliferation and resulted in significant loss of DNA methylation, particularly at enhancers and repetitive elements. Systematic integration of matched in situ Hi-C / PCHi-C, EPIC, RNA-seq and ChIP–seq datasets revealed widespread differences in epigenome regulation and enhancer-promoter communication with Decitabine. We find that loss of DNA methylation with Decitabine strongly affects the open (A) and closed (B) compartment structure and TAD boundary insulation. Our study identified and focused on key DNA methylation-dependent, enhancer ER binding sites that are activated in Decitabine-treated PDX tumours, enabling direct interactions between promoters and multiple distal enhancers, inducing expression of ER target genes and pathways. Overall, we demonstrate that epigenetic therapy inhibits tumour progression through to rewiring of ER-mediated 3D chromatin interactions and transcriptome programs. Our findings suggest that targeting the 3D epigenome with epigenetic therapies represents a promising strategy for anti-cancer treatment in ER+ endocrine resistant breast cancer patients.
 
Overall design To understand the Decitabine-induced molecular changes driving tumour regression on a global scale, we used in situ Hi-C to generate genome-wide 3D genome maps of PDX breast tumours treated with Decitabine. At the same time, we examined the genome-wide DNA methylation (EPIC Microarrays), promoter-anchored interactome (Promoter Capture Hi-C (PCHi-C)), transcription factor binding (ER and FOXA1 ChIP-seq) and gene expression (RNA-seq) in the same tumours.
 
Contributor(s) Achinger-Kawecka J
Citation(s) 38182927
Submission date Mar 29, 2021
Last update date Jan 13, 2025
Contact name Joanna Achinger-Kawecka
E-mail(s) joanna.achinger@adelaide.edu.au
Organization name South Australian Immunogenomics Cancer Institute
Street address AHMS Building, North Terrace
City Adelaide
State/province SA
ZIP/Postal code 5005
Country Australia
 
Platforms (1)
GPL21145 Infinium MethylationEPIC
Samples (8)
GSM5218253 Gar15-13 Vehicle 1_methylation
GSM5218254 Gar15-13 Vehicle 2_methylation
GSM5218255 Gar15-13 Vehicle 3_methylation
This SubSeries is part of SuperSeries:
GSE171074 The potential of epigenetic therapy to target the 3D epigenome in endocrine-resistant breast cancer
Relations
BioProject PRJNA718402

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE171066_Matrix_signal_intensities_Gar15-13.tsv.gz 109.6 Mb (ftp)(http) TSV
GSE171066_RAW.tar 271.8 Mb (http)(custom) TAR (of IDAT)
Processed data included within Sample table

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