Nicotinylation is a histone mark generated from the nicotinic acid metabolite nicotinyl-CoA

Nicotinylation is a histone mark generated from the nicotinic acid metabolite nicotinyl-CoA | 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 Nicotinylation is a histone mark generated from the nicotinic acid metabolite nicotinyl-CoA Hong-Quan Zhang, Yuhan Jiang, Yixiao Li, Lei Zhang, Haoyi Yan, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4384441/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Protein post-translational modifications (PTMs) are crucial for cancer growth and metastasis. Vitamin B3, a key precursor of NAD + and NADP+, however its epigenetic functions in physiology and disease remain unclear. Herein we report a nicotinic acid (NA), a component of vitamin B3, induces a histone PTM, lysine nicotinylation (Knic), and demonstrate 17 Knic site across core histones in cells. Tandem mass spectrometry and stable isotope tracing revealed that NA-derived nicotinyl-CoA, catalysed by ACSS2, enhances histone Knic in vivo and in vitro . Analysis of chromatin accessibility revealed that histone Knic downregulates chromatin accessibility and therefore inhibits gene expression, for instance, restrain the binding of transcription factor HOXB9 to the promoter of oncogene PPFIA1. PPFIA1 level is correlated with malignancy and poor prognosis of hepatocellular carcinoma. These findings suggest that vitamin B3 supplementation may affects the chromatin accessibility depending on its composition. Collectively, we propose that NA induces histone Knic, a histone mark controlling gene expression. Biological sciences/Molecular biology/Post-translational modifications Biological sciences/Cell biology/Post-translational modifications Biological sciences/Chemical biology/Post-translational modifications Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementalinformation1.docx SupplementaryTable1.xlsx Cite Share Download PDF Status: Under Review 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. 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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-4384441","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":300951295,"identity":"48e6e51c-142d-40ba-ab00-4939497ce4e2","order_by":0,"name":"Hong-Quan Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFklEQVRIiWNgGAWjYBACgwNwJg+IsElgbADRbMRrSSNdy+EECAefluO9h1+8bbPLY+A/e/Bzwa/zeczTzhgwfCg7zMA/uwGrFvsz59Is57YlFzMwnEuWntl3u5hxdo4B44xzhxkk7hzAqsXgRo6ZMW8bc2IDY4+BNG/P7cRGoBZm3rbDDAYSCfi01Cc2MPMY/+btOQfR8he/FuPHQDMTG9h4zKR5fhyAaGHEp+XMGTPGOeeOJ7bx8JhZ8zYkA/2SVnCw51w6j8QNHFqO9xh/eFNWndjPf8b4Ns8fuzzD2ckbH/wos5bjn4FdCxCwSYBiBBwRjG0MDIYNDAygoOLBpR4ImD8gZP8wMMjjUToKRsEoGAUjEwAA1tNisPXRX/8AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-8193-0899","institution":"Peking University Health Science Center","correspondingAuthor":true,"prefix":"","firstName":"Hong-Quan","middleName":"","lastName":"Zhang","suffix":""},{"id":300951296,"identity":"7a08bbef-7150-4319-9a79-e410fb50d135","order_by":1,"name":"Yuhan Jiang","email":"","orcid":"","institution":"Peking University Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Yuhan","middleName":"","lastName":"Jiang","suffix":""},{"id":300951297,"identity":"5f9ea84e-b089-4602-b19c-fe04203ed1ad","order_by":2,"name":"Yixiao Li","email":"","orcid":"","institution":"Peking University Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Yixiao","middleName":"","lastName":"Li","suffix":""},{"id":300951298,"identity":"d91d46bb-9bc7-4c52-93ef-b99adb5d8f71","order_by":3,"name":"Lei Zhang","email":"","orcid":"","institution":"Peking University Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Zhang","suffix":""},{"id":300951299,"identity":"ac72269c-c436-406f-a551-9d1b370f3c86","order_by":4,"name":"Haoyi Yan","email":"","orcid":"","institution":"Peking University Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Haoyi","middleName":"","lastName":"Yan","suffix":""},{"id":300951300,"identity":"147da6e9-f957-409b-95b2-a202fdaec544","order_by":5,"name":"Ziheng Qin","email":"","orcid":"","institution":"Peking University Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Ziheng","middleName":"","lastName":"Qin","suffix":""},{"id":300951301,"identity":"210a31d9-6429-4fde-bc16-c073fcc62578","order_by":6,"name":"Qianchen Li","email":"","orcid":"","institution":"Peking University Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Qianchen","middleName":"","lastName":"Li","suffix":""},{"id":300951302,"identity":"92349a7f-227b-4525-855c-c041a536d96e","order_by":7,"name":"Yidi Peng","email":"","orcid":"","institution":"Peking University Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Yidi","middleName":"","lastName":"Peng","suffix":""},{"id":300951303,"identity":"43af06a3-7889-42f2-8295-97c7b4de6121","order_by":8,"name":"Jia Liu","email":"","orcid":"","institution":"Peking University Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Liu","suffix":""},{"id":300951304,"identity":"90bf539c-12cc-4c99-abb1-de392349b989","order_by":9,"name":"Yejing Weng","email":"","orcid":"","institution":"Jingjie PTM Biolab Co.Ltd.","correspondingAuthor":false,"prefix":"","firstName":"Yejing","middleName":"","lastName":"Weng","suffix":""},{"id":300951305,"identity":"81e5dd6c-44d5-46ce-a6a8-e14552b8ab32","order_by":10,"name":"Zhongyi Cheng","email":"","orcid":"","institution":"Jingjie PTM BioLab Co. 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