EXPERIMENT_TITLE: GSM7830695: MCF7_rep2; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Hi-C single-index library preparation of MCF7 cells was performed as previously described [Donaldson-Collier, M.C., et al., EZH2 oncogenic mutations drive epigenetic, transcriptional, and structural changes within chromatin domains. Nature Genetics, 2019. 51(3): p. 517-528.] using MboI (New England Biolabs) restriction enzyme. Single-indexing 75bp Paired-end
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Estrogen Receptor 1 (ESR1; also known as ERa, encoded by ESR1 gene) is the main driver and prime drug target in luminal breast cancer. ESR1 chromatin binding is extensively studied in cell lines and a limited number of human tumors, using consensi of peaks shared among samples. However, little is known about inter-tumor heterogeneity of ESR1 chromatin action, along with its biological implications. Here, we use a large set of ESR1 ChIP-seq data from 70 ESR1+ breast cancers to explore inter-patient heterogeneity in ESR1 DNA binding to reveal a striking inter-tumor heterogeneity of ESR1 action. Of note, commonly shared ESR1 sites show the highest estrogen-driven enhancer activity and are most engaged in long-range chromatin interactions. In addition, the most commonly shared ESR1-occupied enhancers are enriched for breast cancer risk SNP loci. We experimentally confirm SNVs to impact chromatin binding potential for ESR1 and its pioneer factor FOXA1. Finally, in the TCGA breast cancer cohort, we can confirm these variations to associate with differences in expression for the target gene. Cumulatively, we reveal a natural hierarchy of ESR1–chromatin interactions in breast cancers within a highly heterogeneous inter-tumor ESR1 landscape, with the most common shared regions being most active and affected by germline functional risk SNPs for breast cancer development. Overall design: Hi-C was performed on MCF7 breast cancer cell lines in full-media condition. 4 biological replicates have been used.
SAMPLE_TITLE: MCF7_rep2
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "MCF7"}, {"TAG": "cell line", "VALUE": "MCF7"}, {"TAG": "cell type", "VALUE": "breast cancer"}, {"TAG": "geo_loc_name", "VALUE": "missing"}, {"TAG": "collection_date", "VALUE": "missing"}]
Pool_Member_@attributes_sample_title: MCF7_rep2
RUN_SET_RUN_Pool_Member_@attributes_sample_title: MCF7_rep2
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