[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-375903-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-375903-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","epigenetic-deprogramming-by-disruption-of-ciz1-rna-nuclear-assemblies-in-early-stage-breast-cancers","Epigenetic deprogramming by disruption of CIZ1-RNA nuclear assemblies in early-stage breast cancers","","CIZ1 is part of RNA-dependent supramolecular assemblies around the inactive X chromosome (Xi) and smaller nuclear structures. In human breast tumor transcriptomes, the CIZ1 C-terminal anchor domain is elevated even at stage I, correlating with chromatin deprotection and increased lncRNA-containing gene clusters in ~10 Mb cancer-enriched regions. Modeling shows dominant-negative inhibition of CIZ1–Xi reformation after mitosis, producing abnormal assemblies and loss of H2AK119ub1, H3K27me3, and Xist, alongside genomewide expression changes consistent with epigenetic instability that may rapidly deprogram gene expression patterns.",{"@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/epigenetic-deprogramming-by-disruption-of-ciz1-rna-nuclear-assemblies-in-early-stage-breast-cancers/375903/",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/epigenetic-deprogramming-by-disruption-of-ciz1-rna-nuclear-assemblies-in-early-stage-breast-cancers/375903.png","ImageObject",300,407,{"name":42,"@type":43},"Maya Linwood","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-24","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What role does CIZ1 play in inactive X chromosome (Xi) regulation?","Question",{"text":63,"@type":64},"CIZ1 is a component of RNA-dependent supramolecular assemblies (SMACs) associated with Xi. It contributes to maintaining repressed chromatin states and shows unusually high stability within these assemblies.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do CIZ1 levels relate to early-stage breast cancer?",{"text":68,"@type":64},"The CIZ1 C-terminal anchor domain is elevated in human breast tumor transcriptomes even at stage I. This elevation correlates with chromatin deprotection and increased lncRNA-containing gene clusters in cancer-enriched ~10 Mb regions.",{"name":70,"@type":61,"acceptedAnswer":71},"What happens when the CIZ1 C-terminal anchor domain disrupts CIZ1–Xi assemblies?",{"text":72,"@type":64},"Modeling indicates dominant-negative interference with reassembly after mitosis, causing abnormal assemblies similar to those in breast cancer cells. It also leads to depletion of H2AK119ub1, H3K27me3, and Xist, along with consistent genomewide gene expression changes.","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},375903,1790497388,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"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":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"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":113,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","ARTICLE  \nEpigenetic deprogramming by disruption of CIZ1-RNA nuclear assemblies in early-stage breast cancers  \nGabrielle L. Turvey1,2􀀁, Ernesto López de Alba1􀀁, Emma Stewart1,2􀀁, Heather Cook1􀀁, Ahmad Alalti1􀀁, Richard T. Gawne2,3􀀁 , Justin F. -X. Ainscough1,2􀀁, Andrew S. Mason2,3􀀁, and Dawn Coverley1,2􀀁  \nCIZ1 is part of the RNA-dependent supramolecular assemblies that form around the inactive X-chromosome (Xi) in female cells and smaller assemblies throughout the nucleus in both sexes. Here, we show that CIZ1 C-terminal anchor domain (AD) is elevated in human breast tumor transcriptomes, even at stage I. Elevation correlates with deprotection of chromatin and upregulation of lncRNA-containing gene clusters in ∼10 Mb regions enriched in cancer-associated genes. We modeled the effect of AD on endogenous CIZ1–Xi assemblies and observed dominant-negative interference with their reformation after mitosis, leading to abnormal assemblies similar to those in breast cancer cells, and depletion of H2AK119ub1, H3K27me3, and Xist. Consistent alterations in gene expression were evident across the genome, showing that AD-mediated interference has adestabilizing effect, likely by unscheduled exposure of underlying chromatin to modifying enzymes. The data argue for a dominant, potent, and rapid effect of CIZ1 AD that can deprogram gene expression patterns and which may predispose incipient tumors to epigenetic instability.  \nIntroduction  \nSelection and packaging of chromatin into transcriptionally repressed states underlie cell specialization and development. Weakened repression of heterochromatin can result in prooncogenic changes and has the potential to give rise to all the classic hallmarks of cancer, even in the absence of genetic change (Flavahan et al., 2017; Hanahan, 2022; Parreno et al., 2024). The inactive X chromosome (Xi) is the most intensely studied model of facultative heterochromatin formation, revealing how the cis-acting lncRNA Xist (Brockdorff et al., 1992; Brown et al., 1992) directs the formation of large RNA-dependent supramolecular assembly complexes (SMACs) populated by chromatin-modifying enzymes (Markaki et al., 2021). Aggregation of SMAC proteins, mediated by their intrinsically disordered regions (IDRs), creates a functional nuclear compartment that partitions regulatory factors to establish local gene silencing early in development.  \nCip1-interacting zinc finger protein 1 (CIZ1) is one of several proteins that populate Xi SMACs, recruited via its interaction with the repeat E element of Xist (Ridings-Figueroa et al., 2017; Sunwoo et al., 2017) . Several observations set CIZ1 apart from other SMAC components. First, it is not required for Xist  \nrecruitment, Xi silencing, or embryonic development, and the impact of its loss only becomes apparent in somatic cells in which repressed chromatin is already established but must be faithfully maintained. A requirement for CIZ1 is apparent in differentiated fibroblasts from CIZ1 null mice, where local retention ofXist around Xi chromatin is compromised (RidingsFigueroa et al., 2017; Sunwoo et al., 2017), repressive histone posttranslational modifications (PTMs) are lost, and genomewide changes in the expression of genes under the regulation of polycomb repressive complexes (PRC 1 and 2) are apparent (Stewart et al., 2019) . Second, the stability of CIZ1 within Xi SMACs, even those that form during the initiation stages of X-inactivation, is unusually high. Compared with other SMAC components, the residency time ofCIZ1 is estimated to be 2–10-fold longer, similar to that ofXist (Markaki et al., 2021) . Thus, it appears that CIZ1 exchanges less readily than other protein components and might therefore contribute a stabilizing influence on Xist and Xi SMACs.  \nSome of the sequence determinants required for the assembly of CIZ1 within Xi SMACs are known, including two  \n.......................................................................................................","cbCairWR55R8ORg0","https://ap.wps.com/l/cbCairWR55R8ORg0","pdf",8275638,"English","# Introduction\n## Chromatin repression and cancer hallmarks\n## Xi, Xist, and RNA-dependent supramolecular assemblies\n## CIZ1’s role in Xi SMACs\n## CIZ1 sequence features and assembly requirements\n## Xi loss as a cancer hallmark","[{\"question\":\"What role does CIZ1 play in inactive X chromosome (Xi) regulation?\",\"answer\":\"CIZ1 is a component of RNA-dependent supramolecular assemblies (SMACs) associated with Xi. It contributes to maintaining repressed chromatin states and shows unusually high stability within these assemblies.\"},{\"question\":\"How do CIZ1 levels relate to early-stage breast cancer?\",\"answer\":\"The CIZ1 C-terminal anchor domain is elevated in human breast tumor transcriptomes even at stage I. This elevation correlates with chromatin deprotection and increased lncRNA-containing gene clusters in cancer-enriched ~10 Mb regions.\"},{\"question\":\"What happens when the CIZ1 C-terminal anchor domain disrupts CIZ1–Xi assemblies?\",\"answer\":\"Modeling indicates dominant-negative interference with reassembly after mitosis, causing abnormal assemblies similar to those in breast cancer cells. It also leads to depletion of H2AK119ub1, H3K27me3, and Xist, along with consistent genomewide gene expression changes.\"}]","Epigenetic deprogramming by disruption of CIZ1-RNA nuclear assemblies in early-stage breast cancers | PDF",1790216584,76]