FOXN1 remodels chromatin access and schedules fitness during thymus ontogeny

FOXN1 remodels chromatin access and schedules fitness during thymus ontogeny | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article FOXN1 remodels chromatin access and schedules fitness during thymus ontogeny Fatima Dhalla, Andreas Tarcevski, Fabian Klein, Adam Handel, Stefano Maio, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8289212/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The transcription factor FOXN1 is essential for thymic epithelial cell development, function and maintenance. The spatiotemporal dynamics of its expression and the sequential activation of its target gene transcription during thymus organogenesis remain however undefined. Monitoring a fluorescent timer protein serving as a molecular “chronometer” transcriptionally controlled by the Foxn1 locus, we show that FOXN1 expression is spatially controlled during thymus development. Here, FOXN1 progressively opens and remodels the chromatin of its target genes. First supporting a stem and general epithelial cell gene expression profile, extended FOXN1 presence not only conditions the expression of genes indispensable for T cell development and selection but also coincides with the appearance of individual medullary islands. Hence, the length of FOXN1 expression determines a spatially controlled hierarchy of gene expression programs in thymic epithelial cells that orchestrate the capacity to support T lymphopoiesis and the initiation of the thymic medulla. Biological sciences/Immunology/Lymphoid tissues/Thymus Biological sciences/Immunology/Lymphocytes/T cells Thymus Thymic epithelial cells FOXN1 Pioneer factor Full Text Additional Declarations All experimental protocols involving animals were approved an Animal Welfare and Ethical Review Body and the UK Home Office and subsequently carried out in accordance with UK Home Office and Institutional (University of Oxford) regulations, adhering to the principles of the 3R's (Replace, Reduce, Refine) and the ARRIVE guidelines. There is NO Competing Interest. Supplementary Files NIA42021SupplementaryTable1.xlsx Supplementary Table 1 NIA42021SupplementaryTable2.xlsx Supplementary Table 2 NIA42021SupplementaryTable3.xlsx Supplementary Table 3 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8289212","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":566425670,"identity":"0776e8f0-89c8-4029-b4b1-770a1124f4b0","order_by":0,"name":"Fatima 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