{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:12:22Z","timestamp":1793211142075,"version":"4.5.0"},"posted":{"date-parts":[[2025,11,20]]},"group-title":"Neuroscience","reference-count":94,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIDA","award":["R01DA052465"],"award-info":[{"award-number":["R01DA052465"]}]},{"name":"NIH\/NIDA","award":["U18DA052513"],"award-info":[{"award-number":["U18DA052513"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  In classic disease models, removing a pathological insult restores homeostasis. Yet, addiction persists far beyond the period of active drug use. Cocaine abstinence induces changes in gene expression and neuronal signaling in reward-related brain regions that limit recovery during abstinence. We found that 2 weeks of abstinence increased\n                  <jats:italic>Cartpt<\/jats:italic>\n                  (cocaine- and amphetamine-regulated transcript) in the mouse nucleus accumbens and decreased repressive H3K27me3 at the\n                  <jats:italic>Cartpt<\/jats:italic>\n                  locus. While endogenous CART peptide is best described for its anorexigenic function, it is also implicated in human addiction and dopamine homeostasis. To test the causal relevance of\n                  <jats:italic>Cartpt<\/jats:italic>\n                  chromatin remodeling, we used CRISPR-based epigenetic editing tools, dCas9-FOG1 and dCas9-JMJC-ZF, to manipulate H3K27me3 at\n                  <jats:italic>Cartpt in vivo<\/jats:italic>\n                  . Enriching H3K27me3 in D1 neurons repressed\n                  <jats:italic>Cartpt<\/jats:italic>\n                  expression and augmented acquisition and extinction of cocaine preference. These results show that CRISPR epigenetic editing can recapitulate endogenous chromatin states to modulate addiction-related behavior, highlighting broad therapeutic potential of both\n                  <jats:italic>Cartpt<\/jats:italic>\n                  and epigenetic editing.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Abstract Figure<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"689329v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.20.689329","type":"posted-content","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T02:05:17Z","timestamp":1763690717000},"source":"Crossref","is-referenced-by-count":4,"title":["Epigenetic editing of Cartpt promotes acquisition and extinction of cocaine memory"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8518-0167","authenticated-orcid":false,"given":"Julia J.","family":"Winter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol","family":"Hooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keegan S.","family":"Krick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Goldhamer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald W.","family":"DiTullio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle S.","family":"Czarnecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude-Ericka","family":"Ekobeni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiara L.","family":"Rodr\u00edguez-Acevedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon W.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Estill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin D.","family":"Teague","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarthi W.","family":"Ramakrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Nestler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2984-8705","authenticated-orcid":false,"given":"Elizabeth A.","family":"Heller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025112212550835000_2025.11.20.689329v1.1","unstructured":"Substance Abuse and Mental Health Services Administration. 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