{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T16:52:31Z","timestamp":1793811151455,"version":"4.6.1"},"reference-count":37,"publisher":"Society for Neuroscience","issue":"2","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"HHS | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R37DA007359"],"award-info":[{"award-number":["R37DA007359"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["eNeuro"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The transcription factor \u0394FosB has been proposed as a molecular switch for the transition from casual, volitional drug use into a chronically addicted state, but the upstream regulatory mechanisms governing \u0394FosB expression are incompletely understood. In this study, we find a novel regulatory role for the transcription factor E2F3, recently implicated in transcriptional regulation by cocaine, in controlling \u0394FosB induction in the mouse nucleus accumbens (NAc) following cocaine administration. We find that an E2F consensus sequence 500 bp upstream of the<jats:italic>Fosb<\/jats:italic>transcription start site is enriched for E2F3 specifically over other E2F isoforms. We further conclude that \u0394FosB expression is regulated specifically by E2F3a, not E2F3b, that<jats:italic>E2f3a<\/jats:italic>expression is specific to D1 receptor-expressing medium spiny neurons, and that E2F3a overexpression in NAc recapitulates the induction of<jats:italic>Fosb<\/jats:italic>and<jats:italic>\u0394Fosb<\/jats:italic>mRNA expression observed after chronic cocaine exposure. E2F3a knockdown in NAc does not abolish<jats:italic>\u0394Fosb<\/jats:italic>induction by cocaine, a result consistent with previously published data showing that singular knockdown of upstream regulators of \u0394FosB is insufficient to block cocaine-induced expression. Finally, to elucidate potential combinatorial epigenetic mechanisms involved in E2F3a\u2019s regulation of<jats:italic>Fosb<\/jats:italic>, we explore H3K4me3 enrichment at the<jats:italic>Fosb<\/jats:italic>promoter and find that it is not enhanced by E2F3a overexpression, suggesting that it may instead be a pre-existing permissive mark allowing for E2F3a to interact with<jats:italic>Fosb<\/jats:italic>. Together, these findings support a role for E2F3a as a novel, upstream regulator of the addiction-mediating transcription factor \u0394FosB in NAc.<\/jats:p>","DOI":"10.1523\/eneuro.0325-18.2019","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T21:45:12Z","timestamp":1553118312000},"page":"ENEURO.0325-18.2019","source":"Crossref","is-referenced-by-count":24,"title":["<i>Fosb<\/i>Induction in Nucleus Accumbens by Cocaine Is Regulated by E2F3a"],"prefix":"10.1523","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9413-0847","authenticated-orcid":false,"given":"Hannah M.","family":"Cates","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3993-3153","authenticated-orcid":false,"given":"Casey K.","family":"Lardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary 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