{"paper_id":"3dc7a9b7-51ff-4f2a-9a86-2db26c219cbc","body_text":"Linking Chamber-Specific Spatial Chromatin Interactions to Disease Variants and Gene Programs in Human Cardiomyocytes | 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 Linking Chamber-Specific Spatial Chromatin Interactions to Disease Variants and Gene Programs in Human Cardiomyocytes S. Haydar, Rebecca Bednarz, Patrick Laurette, Núria Díaz i Pedrosa, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1897221/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Cell-type specific gene expression programs and response to stimuli are modulated by cis- regulatory elements (CREs). CREs modulate the activity of spatially interacting gene promoters. Heart disease is a major cause of death worldwide. Here, we aim to decode CRE-promoter interactions in atrial and ventricular cardiomyocytes and link them to heart disease and genetic risk factors. Therefore, we analyze the epigenetic features and chromatin interactions of human atrial, ventricular, and failing cardiomyocytes (CM). In failing CM a limited number of genes, including NPPA, showed rewiring events orchestrating differential gene expression. Remarkably, we find that atrial and ventricular CM harbor chamber-specific chromatin interactions which are linked to gene expression indicating that chromatin organization underlies atrial and ventricular CM specification. The chamber-specific chromatin interactions also explain the contribution of non-coding genetic CRE variants to the occurrence of atrial and ventricular diseases, including atrial and ventricular arrhythmia. Functional silencing of CREs carrying genetic QT-duration risk factors confirmed their functional relevance. Our human CM data demonstrates that cell type-specific chromatin interaction analysis provides crucial insights into regulatory mechanisms and aids the interpretation of genetic risk factors identified in patients and association studies. Cardiomyocytes chromatin organization genetic variants heart failure functional genetics Full Text Additional Declarations The authors declare no competing interests. Supplementary Files Supplementalmaterial.pdf Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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-1897221\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":355356760,\"identity\":\"5aec146f-32ca-4f29-a7fe-51fb2eb0af81\",\"order_by\":0,\"name\":\"S. 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