[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-448491-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-448491-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","pervasive-cis-regulatory-co-option-of-a-transposable-element-family-reinforces-cell-identity-across-the-mouse-immune-system","Pervasive cis-regulatory co-option of a transposable element family reinforces cell identity across the mouse immune system","","Transposable elements (TEs) constitute a major fraction of mammalian genomes and contribute broadly to immune regulation, yet their cis-regulatory roles in immune development remain incompletely mapped. This study integrates chromatin accessibility, gene expression, transcription factor occupancy, and DNA-DNA contact data across diverse mouse and human immune cells. It identifies rodent-specific TE subfamilies ORR1E and ORR1D2 that become cell type-specific enhancers throughout the mouse immune system, with lineage-factor-dependent binding changes and evolutionary constraint. ODE-driven genes exhibit cell type- and species-specific expression increases, indicating a TE-to-enhancer functionalization cascade. ",{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/pervasive-cis-regulatory-co-option-of-a-transposable-element-family-reinforces-cell-identity-across-the-mouse-immune-system/448491/",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/pervasive-cis-regulatory-co-option-of-a-transposable-element-family-reinforces-cell-identity-across-the-mouse-immune-system/448491.png","ImageObject",300,407,{"name":42,"@type":43},"Rhys","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-06","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",6,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What question does the study address about transposable elements?","Question",{"text":63,"@type":64},"The study investigates what drives specific TE loci or families to be co-opted as cis-regulatory elements during evolution, particularly across immune cell development.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which transposable element subfamilies are identified in the work?",{"text":68,"@type":64},"The authors identify two rodent-specific TE subfamilies, ORR1E and ORR1D2, collectively termed ODE.",{"name":70,"@type":61,"acceptedAnswer":71},"How do ODE loci function in immune cells?",{"text":72,"@type":64},"ODE loci transform into cell type-specific enhancers, where acquired post-insertion mutations enable differential binding of lineage-specifying transcription factors and regulate hundreds of immune-related genes.","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},448491,1790965413,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,105,110,114,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"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":111,"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},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","bioRxiv preprint doi: [https://doi.org/10.64898/2025.12.22.696042](https://doi.org/10.64898/2025.12.22.696042); this version posted December 25, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC 4.0 International license.  \n1 Pervasive cis-regulatory co-option of a transposable element family reinforces cell identity  \n2 across the mouse immune system  \n3  \n4 Jason D. Chobirko 1, Cédric Feschotte 1* and Andrew Grimson1* 5  \n6 1Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA  \n7 *Contributed equally  \n8  \n9 Corresponding authors: [agrimson@cornell.edu](agrimson@cornell.edu) (A.G.) [and](and cf458@cornell.edu)[ ](and cf458@cornell.edu)[cf458@cornell.edu](and cf458@cornell.edu) (C.F.)  \n10  \nbioRxiv preprint doi: [https://doi.org/10.64898/2025.12.22.696042](https://doi.org/10.64898/2025.12.22.696042); this version posted December 25, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC 4.0 International license.  \n11 Abstract  \n12 Transposable elements (TEs) make up about half of the human and mouse genomes and play  \n13 important regulatory roles in immune responses. However, the cis-regulatory contribution of TEs  \n14 to immune cell development is less characterized. Here, we analyzed hundreds of chromatin  \n15 accessibility, gene expression, transcription factor occupancy and DNA-DNA contact datasets in  \n16 diverse mouse and human immune cells. We identified two rodent-specific TE subfamilies,  \n17 ORR1E and ORR1D2 (collectively, ODE) that have transformed into cell type-specific  \n18 enhancers across the mouse immune system. ODE loci acquired mutations post-insertion that  \n19 enable differential binding of lineage-specifying transcription factors. ODEs show evidence of  \n20 evolutionary sequence constraint and contact promoters of hundreds of genes in immune cells.  \n21 ODE-targeted genes show cell type-specific and mouse-specific increases in expression  \n22 compared to concordant human cell types. Thus, a single TE family can undergo  \n23 functionalization after its genomic spread to generate batteries of cell-specific enhancers  \n24 supporting a complex developmental cascade.  \n25  \nbioRxiv preprint doi: [https://doi.org/10.64898/2025.12.22.696042](https://doi.org/10.64898/2025.12.22.696042); this version posted December 25, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC 4.0 International license.  \n26 Introduction  \n27 Transposable elements (TEs) are mobile elements capable of selfish propagation within  \n28 genomes. TEs are found in nearly all organisms and make up a large percentage of the human  \n29 (~54%) [1] and mouse (~40%) [2] genomes. To facilitate their propagation, TEs often harbor  \n30 regulatory sequences – promoters and enhancers – with multiple transcription factor (TF)  \n31 binding sites driving the expression of TE-encoded genes [3,4] . This reliance on host TFs for  \n32 propagation has evolutionarily tied TEs to their hosts, leading to species-specific TE expansions  \n33 and distinct repertoires across species [5] . Notably, a sizable fraction of TEs in human (~24%)  \n34 and mouse (~32%) are unique to the primate and rodent lineages, respectively [2] . Thus, lineage- 35 specific amplification of TEs make them compelling candidates to introduce cis-regulatory  \n36 elements (CREs) that impact proximal gene expression, rewire networks and drive phenotypic  \n37 changes between species [3,4,6] . However, most TE insertions have neutral or detrimental effects  \n38 on ho","cbCainssxei8nf6p","https://ap.wps.com/l/cbCainssxei8nf6p","pdf",8181553,66,"English","# Abstract\n# Introduction\n## Transposable elements as regulatory substrates\n## Immune system development and TE co-option gap\n## Study objective and datasets","[{\"question\":\"What question does the study address about transposable elements?\",\"answer\":\"The study investigates what drives specific TE loci or families to be co-opted as cis-regulatory elements during evolution, particularly across immune cell development.\"},{\"question\":\"Which transposable element subfamilies are identified in the work?\",\"answer\":\"The authors identify two rodent-specific TE subfamilies, ORR1E and ORR1D2, collectively termed ODE.\"},{\"question\":\"How do ODE loci function in immune cells?\",\"answer\":\"ODE loci transform into cell type-specific enhancers, where acquired post-insertion mutations enable differential binding of lineage-specifying transcription factors and regulate hundreds of immune-related genes.\"}]","Pervasive cis-regulatory co-option of a transposable element family reinforces cell identity across the mouse immune system | PDF",1790727363,166]