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Co-immunoprecipitation identifies TLE co-repressors and HES1 as potential interactors, supported by structural modeling of truncated KDM6A with TLE, HES1, RUNX, and HHEX. Results support studying KDM6A functions independent of demethylase activity, advancing understanding of KDM6A malfunction in bladder cancer.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/differential-occupancy-and-regulatory-interactions-of-kdm6a-in-bladder-cell-lines/377688/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/differential-occupancy-and-regulatory-interactions-of-kdm6a-in-bladder-cell-lines/377688.png","ImageObject",300,407,{"name":42,"@type":43},"Finn","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the central focus regarding KDM6A in this study?","Question",{"text":63,"@type":64},"The study investigates how KDM6A function differs between normal, immortalized, and cancerous bladder cell lines, emphasizing occupancy and regulatory interactions.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does the paper characterize KDM6A occupancy across cell types?",{"text":68,"@type":64},"It identifies KDM6A genomic occupancy patterns that vary by cell type and by the mutation status of KDM6A, particularly in genes tied to differentiation, chromatin organization, and Notch signaling.",{"name":70,"@type":61,"acceptedAnswer":71},"What molecular features and interactions are highlighted in T24 cells?",{"text":72,"@type":64},"Transcription factor motif analysis shows HES1 enrichment at KDM6A peaks in T24 cells, where KDM6A contains a truncating mutation lacking a demethylase domain. Co-immunoprecipitation suggests interactions involving TLE co-repressors and HES1, supported by structural modeling.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},377688,1790734170,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","cells  \nArticle  \nDifferential Occupancy and Regulatory Interactions of KDM6Ain Bladder Cell Lines  \nGülden Özden-Yılmaz 1, Busra Savas 1,2, Ahmet Bursalı 1, Aleyna Eray 1,2, Alirıza Arıba¸s 1, Serif Senturk 1,2, Ezgi Karaca 1,2, Gökhan Karakülah 1,2 and Serap Erkek-Ozhan 1, *  \nCitation: Özden-Yılmaz, G.; Savas, B.; Bursalı, A.; Eray, A.; Arıba¸s, A.; Senturk, S.; Karaca, E.; Karakülah, G.; Erkek-Ozhan, S. Differential Occupancy and Regulatory Interactions of KDM6A in Bladder Cell Lines. Cells 2023, 12, 836 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells12060836  \nAcademic Editors: Yinghui Li and Kamalakshi Deka  \nReceived: 19 December 2022  \nRevised: 16 February 2023  \nAccepted: 1 March 2023  \nPublished: 8 March 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Izmir Biomedicine and Genome Center, Inciralti, 35340 Izmir, Turkey  \n2 Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Inciralti, 35340 Izmir, Turkey  \n* Correspondence: [serap.erkek@ibg.edu.tr](serap.erkek@ibg.edu.tr)  \nAbstract: Epigenetic deregulation is a critical theme which needs further investigation in bladder cancer research. One of the most highly mutated genes in bladder cancer is KDM6A, which functions as an H3K27 demethylase and is one of the MLL3/4 complexes. To decipher the role of KDM6A in normal versus tumor settings, we identified the genomic landscape of KDM6A in normal, immortalized, and cancerous bladder cells. Our results showed differential KDM6A occupancy in the genes involved in cell differentiation, chromatin organization, and Notch signaling depending on the cell type and the mutation status of KDM6A. Transcription factor motif analysis revealed HES1 to be enriched at KDM6A peaks identified in the T24 bladder cancer cell line; moreover, it has a truncating mutation in KDM6A and lacks a demethylase domain. Our co-immunoprecipitation experiments revealed TLE co-repressors and HES1 as potential truncated and wild-type KDM6A interactors. With the aid of structural modeling, we explored how truncated KDM6A could interact with TLE and HES1, as well as RUNX and HHEX transcription factors. These structures provide a solid means of studying the functions of KDM6A independently of its demethylase activity. Collectively, our work provides important contributions to the understanding of KDM6A malfunction in bladder cancer.  \nKeywords: KDM6A; bladder cancer; chromatin regulation; protein–protein interactions; structural modeling  \n1. Introduction  \nChromatin deregulation is regarded as one of the hallmarks of cancer; it is reflected at multiple different levels and affects many processes that drive tumorigenesis [1] . Malfunction in epigenetic regulatory mechanisms is especially noteworthy in bladder cancer considering the prominently high rate of mutations in chromatin-modifier genes [2], which underscores the importance of studying epigenetic regulation in this cancer type.  \nBladder cancer is one of the most common and lethal diseases worldwide. Each year, there are 430,000 cases of patients diagnosed with bladder cancer, 170,000 of which result in death [3] . In total, 75–80% of bladder cancers show non-muscle-invasive characteristics, while the remaining are muscle-invasive [2] . Despite recent genomic and molecular characterizations, cisplatin-based chemotherapy and radiotherapy-based approaches still remain the main treatment options for this cancer type [4] . Thus, within the context of highchromatin-modifier mutations in this cancer [2], the identification of epigenetic signatures implicated in pathogenesis of this disease is crucial.  \nAmong the chromatin-modifier mut","cbCaikhfjoI6bYdS","https://ap.wps.com/l/cbCaikhfjoI6bYdS","pdf",4324644,22,"English","# Abstract\n# Introduction\n## Chromatin deregulation and bladder cancer burden\n## Chromatin-modifier mutations and KDM6A features\n## Known functions of KDM6A in epigenetic regulation","[{\"question\":\"What is the central focus regarding KDM6A in this study?\",\"answer\":\"The study investigates how KDM6A function differs between normal, immortalized, and cancerous bladder cell lines, emphasizing occupancy and regulatory interactions.\"},{\"question\":\"How does the paper characterize KDM6A occupancy across cell types?\",\"answer\":\"It identifies KDM6A genomic occupancy patterns that vary by cell type and by the mutation status of KDM6A, particularly in genes tied to differentiation, chromatin organization, and Notch signaling.\"},{\"question\":\"What molecular features and interactions are highlighted in T24 cells?\",\"answer\":\"Transcription factor motif analysis shows HES1 enrichment at KDM6A peaks in T24 cells, where KDM6A contains a truncating mutation lacking a demethylase domain. Co-immunoprecipitation suggests interactions involving TLE co-repressors and HES1, supported by structural modeling.\"}]","Differential Occupancy and Regulatory Interactions of KDM6A in Bladder Cell Lines | PDF",1790226678,55]