EXPERIMENT_TITLE: GSM5218302: Gar15-13 Vehicle 2_HiC; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Hi-C experiments were performed on fresh-frozen tumour samples using the Arima Hi-C+ kit (Arima Genomics, Inc.) with minor modifications. Hi-C libraries were prepared using the Swift Biosciences Accel-NGS 2S Plus DNA Library Kit with a modified protocol provided by Arima.
STUDY_DESCRIPTOR_STUDY_ABSTRACT: 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.
SAMPLE_TITLE: Gar15-13 Vehicle 2_HiC
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "Gar15-13 Vehicle tumour"}, {"TAG": "tissue", "VALUE": "Breast cancer PDX model Gar15-13"}, {"TAG": "treatment", "VALUE": "Vehicle"}, {"TAG": "replicate", "VALUE": "2"}]
Pool_Member_@attributes_sample_title: Gar15-13 Vehicle 2_HiC
RUN_SET_RUN_Pool_Member_@attributes_sample_title: Gar15-13 Vehicle 2_HiC
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