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Using 70 ESR1+ human breast cancers with ESR1 ChIP-seq, the study reveals striking inter-patient heterogeneity in ESR1 DNA binding and associated enhancer activity, including long-range chromatin interactions at commonly shared sites. Shared enhancers are enriched for breast cancer risk SNP loci, and experimental validation links SNVs to altered chromatin binding potential for ESR1 and FOXA1, with TCGA results connecting these variations to expression differences.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/estrogen-receptor-1-chromatin-profiling-in-human-breast-tumors-reveals-high-inter-patient-heterogeneity-with-enrichment-of-risk-snps-and-enhancer-activity-at-most-conserved-regions/332117/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/estrogen-receptor-1-chromatin-profiling-in-human-breast-tumors-reveals-high-inter-patient-heterogeneity-with-enrichment-of-risk-snps-and-enhancer-activity-at-most-conserved-regions/332117.png","ImageObject",300,407,{"name":92,"@type":93},"Ivy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does the study investigate about ESR1 in breast cancer?","Question",{"text":112,"@type":113},"It examines inter-patient heterogeneity in ESR1 chromatin action, focusing on ESR1 DNA binding, enhancer activity, and long-range chromatin interactions in human breast tumors.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the researchers assess ESR1 binding differences across patients?",{"text":117,"@type":113},"They used a large set of ESR1 ChIP-seq data from 70 ESR1+ breast cancers to analyze ESR1 DNA binding patterns and their functional consequences.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the relationship between risk SNPs and ESR1 regulatory regions?",{"text":121,"@type":113},"Commonly shared ESR1-occupied enhancers are enriched for breast cancer risk SNP loci, and validated SNVs can influence chromatin binding potential for ESR1 and FOXA1.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},332117,1790012835,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","Estrogen receptor 1 chromatin profiling in human breast tumors reveals high inter-patient heterogeneity with enrichment of risk SNPs and enhancer activity at most-conserved regions  \nStacey E. P. Joosten, 1,2,14 Sebastian Gregoricchio, 1,2,14 Suzan Stelloo,2,3 Elif Yap ıcı,4,5 Chia-Chi Flora Huang,6 Kerim Yavuz,6 Maria Donaldson Collier, 1,2 Tunç Morova,6 Umut Berkay Altinta,6 Yongsoo Kim, 7 Sander Canisius,8,9 Cathy B. Moelans, 10 Paul J. van Diest,10 Gozde Korkmaz,4,5 Nathan A. Lack,4,5,6 Michiel Vermeulen,2,3,11 Sabine C. Linn,8,10,12 and Wilbert Zwart 1,2,13  \n1Division of Oncogenomics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; 2 Oncode Institute, The Netherlands; 3Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, 6500HB Nijmegen, The Netherlands; 4Koç University School of Medicine, 34450 Istanbul, Turkey; 5Koç University Research Center for Translational Medicine (KUTTAM), 34450 Istanbul, Turkey; 6 Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, V6H 3Z6 Canada; 7Department of Pathology, Amsterdam University Medical Center, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands; 8Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; 9Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; 10Department of Pathology, Utrecht University Medical Centre, 3584 CX Utrecht, The Netherlands; 11Division of Molecular Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; 12Department of Medical Oncology, Antoni van Leeuwenhoek Hospital, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; 13Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands  \nEstrogen Receptor 1 (ESR1; also known as ERα, 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.  \n[Supplemental material is available for this article.]  \nThe Estrogen Receptor 1 (ESR1; also known as ERα, encoded by the ESR1 gene) is the driving force in most breast cancers diagnosed in women—as well as men—worldwide (Waks and Winer 2019) . As such, ESR1 is considered the critical drug target in both the adjuvant and metastatic phase of the disease, but resistance to hormonal treatment is common (Early Breast Cancer Trialists’ Collaborative Group [EBCTCG] 2005) . ESR1 serves as a hormone-dependent transcription factor (TF), associating to DNA regulatory elements upon ligand-mediated activation to drive activity of responsive genes, ul-  \ntimately giving rise to tumor growth. DNA binding","cbCaifWEYGOTeCGL","https://ap.wps.com/l/cbCaifWEYGOTeCGL","pdf",8267072,17,"English","# Background\n## ESR1 as a driver and drug target\n## ESR1 DNA binding and enhancer elements\n# Methods\n## ESR1 ChIP-seq in human breast cancers\n## Chromatin interaction and enhancer activity assessment\n## SNV validation and TCGA association\n# Key findings\n## Inter-patient heterogeneity of ESR1 action\n## Shared ESR1 sites and enhancer activity\n## Enrichment of breast cancer risk SNP loci\n# Implications","[{\"question\":\"What does the study investigate about ESR1 in breast cancer?\",\"answer\":\"It examines inter-patient heterogeneity in ESR1 chromatin action, focusing on ESR1 DNA binding, enhancer activity, and long-range chromatin interactions in human breast tumors.\"},{\"question\":\"How did the researchers assess ESR1 binding differences across patients?\",\"answer\":\"They used a large set of ESR1 ChIP-seq data from 70 ESR1+ breast cancers to analyze ESR1 DNA binding patterns and their functional consequences.\"},{\"question\":\"What is the relationship between risk SNPs and ESR1 regulatory regions?\",\"answer\":\"Commonly shared ESR1-occupied enhancers are enriched for breast cancer risk SNP loci, and validated SNVs can influence chromatin binding potential for ESR1 and FOXA1.\"}]","Estrogen receptor 1 chromatin profiling in human breast tumors reveals high inter-patient heterogeneity with enrichment of risk SNPs and enhancer activity at most-conserved regions | PDF",1789996877,43]