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The study discovers ER and ZMIZ1 within the same assembly using quantitative proteomics and validates the interaction with proximity ligation assays. ER-positive cancer models show reduced proliferation after ZMIZ1 loss, while RNA-seq time-course analyses reveal a delay in estradiol-induced cell cycle gene responses. ENCODE integration supports ER and ZMIZ1 binding at the E2F2 promoter, proposing an ER-ZMIZ1-E2F2 signaling axis and linking high ZMIZ1 to worse patient outcomes.",{"@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/zmiz1-enhances-er-dependent-expression-of-e2f2-in-breast-cancer/342814/",{"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/zmiz1-enhances-er-dependent-expression-of-e2f2-in-breast-cancer/342814.png","ImageObject",300,407,{"name":92,"@type":93},"Eliana","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does ZMIZ1 play in ER-positive breast cancer cells?","Question",{"text":112,"@type":113},"ZMIz1 loss significantly decreases proliferation in ER-positive cancer cell lines, indicating a functional contribution to ER-driven growth.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the study assess the ER–ZMIZ1 interaction?",{"text":117,"@type":113},"ER and ZMIZ1 were identified in the same multi-protein assembly using quantitative proteomics and validated with a proximity ligation assay.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanism does the study propose for ZMIZ1’s effect on gene regulation?",{"text":121,"@type":113},"The data support a novel ZMIZ1–ER–E2F2 signaling axis in which ER and ZMIZ1 enable an efficient estrogenic response at a subset of cell-cycle genes, including via promoter binding at E2F2.","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},342814,1790167358,{"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":8,"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},4398048949847,"https://ap-avatar.wpscdn.com/avatar/400002536579ef2da7f?_k=1778318612642679267","Journal of  \nMolecular Endocrinology (2024) 73 e230133  \n[https://doi.org/10.1530/JME-23-0133](https://doi.org/10.1530/JME-23-0133)  \nRESEARCH  \nReceived 7 November 2023 Accepted 2 April 2024 Available online 2 April 2024  \nVersion of Record published 25 April 2024  \n\n| ZMIZ1 enhances ERα-dependent expression of E2F2 in breast cancer\u003Cbr>Weiye Zhao1, Susanna F Rose1, Ryan Blake2, Aňze Godicelj3, Amy E Cullen2, Jack Stenning1,\u003Cbr>Lucy Beevors4, Marcel Gehrung2, Sanjeev Kumar5, Kamal Kishore2, Ashley Sawle2, Matthew Eldridge2, Federico M Giorgi6, Katherine S Bridge1,7, Florian Markowetz2 and Andrew N Holding1,7,8\u003Cbr>1Department of Biology, University of York, York, UK\u003Cbr>2CRUK Cambridge Institute, University of Cambridge, Cambridge, UK\u003Cbr>3Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Smith Building, Boston, Massachusetts, USA\u003Cbr>4The Institute of Metabolism and Systems Research (IMSR), University of Birmingham, College of Medical and Dental Sciences, Birmingham, UK\u003Cbr>5Chris O’Brien Lifehouse, Sydney, New South Wales, Australia\u003Cbr>6Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy\u003Cbr>7York Biomedical Research Institute, University of York, York, UK\u003Cbr>8The Alan Turing Institute, Kings Cross, London, UK\u003Cbr>Correspondence should be addressed to F Markowetz or A N Holding: [florian. markowetz@cruk.cam.ac.uk](florian. markowetz@cruk.cam.ac.uk) [or](or Andrew. Holding@york.ac. uk)[ Andrew. Holding@york.ac. uk](or Andrew. Holding@york.ac. uk) |\n| --- |\n| Abstract\u003Cbr>The estrogen receptor-α (ER) drives 75% of breast cancers. On activation, the ER recruits and assembles a 1–2 MDa transcriptionally active complex. These complexes can modulate tumour growth, and understanding the roles of individual proteins within these complexes can help identify new therapeutic targets. Here, we present the discovery of ER and ZMIZ1 within the same multi-protein assembly by quantitative proteomics, and validated by proximity ligation assay. We characterise ZMIZ1 function by demonstrating a significant decrease in the proliferation of\u003Cbr>ER-positive cancer cell lines. To establish a role for the ER-ZMIZ1 interaction, we measured the transcriptional changes in the estrogen response post-ZMIZ1 knockdown using an RNA-seq time-course over 24 h. Gene set enrichment analysis of the ZMIZ1-knockdown data identified a specific delay in the response of estradiol-induced cell cycle genes. Integration of ENCODE data with our RNA-seq results identified that ER and ZMIZ1 both bind the promoter of E2F2 . We therefore propose that ER and ZMIZ1 interact to enable the efficient estrogenic response at subset of cell cycle genes via a novel ZMIZ1–ER–E2F2 signalling axis. Finally, we show that high ZMIZ1 expression is predictive of worse patient outcome, ER and ZMIZ1 are co-expressed in breast cancer patients in TCGA and METABRIC, and the proteins are co-localised within the nuclei of tumour cell in patient biopsies. In conclusion, we establish that ZMIZ1 is a regulator of the estrogenic cell cycle response and provide evidence of the biological importance of the ER–ZMIZ1 interaction in ER-positive patient tumours, supporting potential clinical relevance. |\n| Keywords: breast cancer; cancer; co-factors transcription nuclear receptors signalling patient outcome; E2F2; estrogen receptor; ZMIZ1 |\n|  |\n\nPublished by Bioscientifica Ltd.  \n[https://jme.bioscientifica.com](https://jme.bioscientifica.com)  \n© 2024 the author(s)  \nThis work is licensed under a Creative Commons Attribution 4.0 International License.  \nW Zhao et al.  \nJournal of Molecular Endocrinology (2024) 73 e230133  \n[https://doi.org/10.1530/JME-23-0133](https://doi.org/10.1530/JME-23-0133)  \nIntroduction  \nApproximately 75% of breast cancers are classified as estrogen receptor-α (ER) positive. In these cancers, the ER is no longer correctly regulated, subverts cell division regulation, and becomes the driving transcription factor in the tumour (Mohammed","cbCaiaXHZKM75q8D","https://ap.wps.com/l/cbCaiaXHZKM75q8D","pdf",6589886,14,"English","# Abstract\n# Introduction\n## Estrogen receptor-α in ER-positive breast cancer\n# The ER transcriptional complex\n## Enhancer binding and transcriptional complex formation\n# Further characterization of ER-interacting proteins\n## Cofactor-based therapeutic relevance","[{\"question\":\"What role does ZMIZ1 play in ER-positive breast cancer cells?\",\"answer\":\"ZMIz1 loss significantly decreases proliferation in ER-positive cancer cell lines, indicating a functional contribution to ER-driven growth.\"},{\"question\":\"How did the study assess the ER–ZMIZ1 interaction?\",\"answer\":\"ER and ZMIZ1 were identified in the same multi-protein assembly using quantitative proteomics and validated with a proximity ligation assay.\"},{\"question\":\"What mechanism does the study propose for ZMIZ1’s effect on gene regulation?\",\"answer\":\"The data support a novel ZMIZ1–ER–E2F2 signaling axis in which ER and ZMIZ1 enable an efficient estrogenic response at a subset of cell-cycle genes, including via promoter binding at E2F2.\"}]","ZMIZ1 enhances ERα-dependent expression of E2F2 in breast cancer | PDF",1790048303,35]