Cell type-specific functions of the PBAF chromatin-remodeling complex in neuronal diversification

Cell type-specific functions of the PBAF chromatin-remodeling complex in neuronal diversification | 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 Cell type-specific functions of the PBAF chromatin-remodeling complex in neuronal diversification Anthony Osuma, Yinan Li, Seth Taylor, Manasa Prahlad, Laura Mathies, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5370605/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Dec, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract The mammalian SWI/SNF family of chromatin remodelers includes the BAF and PBAF complexes, mutations in which cause various neurodevelopmental conditions. Although BAF activity is required at multiple steps of nervous system development, the specific neural functions of PBAF remain largely unexplored. Through an unbiased genetic screen in C. elegans, we identify here critical roles for PBAF in postmitotic neuronal identity. In nerve cord motor neurons (MNs), PBAF represses gene expression by antagonizing the terminal selector-type transcription factor UNC-3 (EBF1-4). In contrast, PBAF activates gene expression in posteriorly located MNs. This dichotomy in PBAF function generates distinct MN identities. Genetic evidence suggests that the cell type-specific functions of PBAF in different MN groups arise via its recruitment to specific gene loci by conserved transcription factors. Altogether, our findings provide a conceptual framework to understand specific neuronal defects that arise in neurological conditions caused by mutations in broadly expressed chromatin-remodeling complexes. Biological sciences/Developmental biology/Neurogenesis Biological sciences/Neuroscience/Development of the nervous system Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplInfoFiguresandlegends.pdf Cite Share Download PDF Status: Published Journal Publication published 14 Dec, 2025 Read the published version in Nature Communications → 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-5370605","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":374273465,"identity":"e73af4ad-82ab-4b0d-a5fa-b1d5399cf41f","order_by":0,"name":"Anthony Osuma","email":"","orcid":"","institution":"University of Chicago","correspondingAuthor":false,"prefix":"","firstName":"Anthony","middleName":"","lastName":"Osuma","suffix":""},{"id":374273466,"identity":"55c7e867-1a93-4c92-bfe4-c0c5d1aced06","order_by":1,"name":"Yinan Li","email":"","orcid":"","institution":"University of 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