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This study reveals a chromatin-associated function of LINE-1 RNA, the only autonomous retrotransposon in the human genome. Subcellular-resolved transcriptomics shows LINE-1 RNAs are mainly nascent transcripts from full-length, cell type–specific loci. A long-read chromosome conformation assay identifies highly interactive LINE-1 loci required for oncogenic gene expression, where transcription-dependent chromatin interactions arise and LINE-1 RNA depletion disrupts them. ",{"@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/line-1-locus-transcription-nucleates-oncogenic-chromatin-architecture/352678/",{"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/line-1-locus-transcription-nucleates-oncogenic-chromatin-architecture/352678.png","ImageObject",300,407,{"name":92,"@type":93},"WPS_1786070896","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main finding about LINE-1 RNAs in cancer cells?","Question",{"text":112,"@type":113},"LINE-1 RNAs primarily exist as chromatin-associated nascent transcripts produced from full-length, cell type–specific genomic copies. This links LINE-1 locus transcription to oncogenic gene control beyond mutagenesis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the study assess chromatin interactions at LINE-1 loci?",{"text":117,"@type":113},"The study used a long-read chromosome conformation assay to identify a class of highly interactive LINE-1 loci. These loci are required for gene expression across cancer subtypes.",{"name":119,"@type":110,"acceptedAnswer":120},"What happens when LINE-1 RNA is depleted or when LINE-1 is reintroduced?",{"text":121,"@type":113},"LINE-1 RNA depletion disrupts LINE-1–centric chromatin interactions and downregulates associated genes. Genomic insertion of an inducible LINE-1 generates de novo chromatin interactions in a transcription-dependent manner.","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},352678,1790230676,{"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":81,"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},549768072016,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","ReseaRch aRticle  \nLINE-1 Locus Transcription Nucleates Oncogenic Chromatin Architecture   \nMichael Lee Jr1, Yuannyu Zhang2, Jun Yi Stanley Lim1, Tao Dai1, James Ye3, Margaret B. Cervantes1, Varun Sondhi1, Sisi Zheng4, Yoon Jung Kim1, Brandon Chen1, Ralph J. DeBerardinis1,4,5,6,7, and Jian Xu2  \nRetrotransposons are genomic parasites frequently reactivated in cancers, in  \nwhich their mobility can cause genetic alterations. However, it remains unclear whether their gene products contribute to cancer beyond mutagenesis. In this study, we uncover a chromatin-associated function of RNAs from long interspersed element-1 (LINE-1), the only autonomous retrotransposon in the human genome. Subcellular-resolved transcriptomics revealed that LINE-1 RNAs are primarily nascent transcripts produced by full-length, cell type–specific genomic copies of evolutionarily young subfamilies. Using a long-read chromosome conformation assay, we identified a class of highly interactive LINE-1 loci required for gene expression across cancer subtypes, revealing an unexpected regulatory role for LINE-1 locus transcription in oncogenic gene control. LINE-1 RNA depletion disrupted LINE-1–centric chromatin interactions and downregulated associated genes, whereas genomic insertion of an inducible LINE-1 generated de novo chromatin interactions in a transcription-dependent manner. Therefore, beyond their mutagenic potential, retrotransposons also regulate cancer gene expression by nucleating chromatin architecture through their transcriptional activity.  \nSIgNIfICANCE: We developed a long-read chromatin conformation assay capable of resolving repetitive DNA, enabling the identification of highly interactive LINE-1 retrotransposon loci that nucleate chromatin architecture in cancer cells. This activity is driven by chromatin-associated LINE-1 transcripts, offering a biological rationale for the frequent reactivation of LINE-1 transcription in cancer.  \nintRoduction  \nMore than half of the human genome is composed of interspersed repeats derived from mobile genomic parasites known as transposable elements (TE) or transposons. The long interspersed element-1 (LINE-1) retrotransposon family is the only autonomously active TE in humans. Although most LINE-1 sequences are truncated or mutated remnants of ancient insertions, about 10,000 full-length loci persist. Of these, approximately 100 genomic copies remain capable of retrotransposition, the process by which LINE-1 integrates into new genomic locations via an RNA intermediate (1–3) . Intact LINE-1 elements encode two open reading frames  \n1Children’s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas. 2Center of Excellence for Leukemia Studies, Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee. 3Department of Molecular Biology, UT Southwestern Medical Center, Dallas, Texas. 4Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas. 5Harold  \nC. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas. 6Eugene McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, Texas.  \n7Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas.  \nM. Lee Jr and Y. Zhang contributed equally to this article.  \nCorresponding Author: Jian Xu, St. Jude Children’s Research Hospital, 262 Danny Thomas Place – MS 345, Memphis, TN 38105. E-mail: [jian.xu@stjude.org](jian.xu@stjude.org)  \nCancer Discov 2026;16:800–21  \ndoi: 10. 1158/2159-8290 . CD-25-1085  \nThis open access article is distributed under the Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.  \n©2026 The Authors; Published by the American Association for Cancer Research  \n(ORF) which produce proteins essential for de novo retrotransposition: ORF1p, a 40 kDa RNA chaperone with poorly understood functions (4), and ORF2p, a 150 kDa pr","cbCaipVgoOyt3dmv","https://ap.wps.com/l/cbCaipVgoOyt3dmv","pdf",17781560,22,"English","# Introduction\n## LINE-1 in the human genome and cancer\n## LINE-1 RNAs as chromatin-associated nascent transcripts\n# Methods and assays\n## Subcellular-resolved transcriptomics and smRNA-FISH\n## Long-read chromosome conformation assay\n# Results and significance\n## Highly interactive LINE-1 loci and transcription-dependent regulation","[{\"question\":\"What is the main finding about LINE-1 RNAs in cancer cells?\",\"answer\":\"LINE-1 RNAs primarily exist as chromatin-associated nascent transcripts produced from full-length, cell type–specific genomic copies. This links LINE-1 locus transcription to oncogenic gene control beyond mutagenesis.\"},{\"question\":\"How did the study assess chromatin interactions at LINE-1 loci?\",\"answer\":\"The study used a long-read chromosome conformation assay to identify a class of highly interactive LINE-1 loci. These loci are required for gene expression across cancer subtypes.\"},{\"question\":\"What happens when LINE-1 RNA is depleted or when LINE-1 is reintroduced?\",\"answer\":\"LINE-1 RNA depletion disrupts LINE-1–centric chromatin interactions and downregulates associated genes. Genomic insertion of an inducible LINE-1 generates de novo chromatin interactions in a transcription-dependent manner.\"}]","LINE-1 Locus Transcription Nucleates Oncogenic Chromatin Architecture | PDF",1790100805,55]