{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T02:31:25Z","timestamp":1773109885892,"version":"3.50.1"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","award":["T32DA028874"],"award-info":[{"award-number":["T32DA028874"]}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","award":["DP1 DA044250"],"award-info":[{"award-number":["DP1 DA044250"]}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","award":["1R01DA052465-01A1"],"award-info":[{"award-number":["1R01DA052465-01A1"]}]},{"name":"Penn | School of Arts and Sciences, University of Pennsylvania","award":["The Endowed Dean\u2019s Research Award"],"award-info":[{"award-number":["The Endowed Dean\u2019s Research Award"]}]},{"name":"Penn | Perelman School of Medicine, University of Pennsylvania","award":["Pilot Award: Epigenetic Institute"],"award-info":[{"award-number":["Pilot Award: Epigenetic Institute"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cocaine epigenetically regulates gene expression via changes in histone post-translational modifications (HPTMs). We previously found that the immediate early gene\n                    <jats:italic>Nr4a1<\/jats:italic>\n                    is epigenetically activated by cocaine in mouse brain reward regions. However, few studies have examined multiple HPTMs at a single gene. Bivalent gene promoters are simultaneously enriched in both activating (H3K4me3 (K4)) and repressive (H3K27me3 (K27)) HPTMs. As such, bivalent genes are lowly expressed but poised for activity-dependent gene regulation. In this study, we identified K4&amp;K27 bivalency at\n                    <jats:italic>Nr4a1<\/jats:italic>\n                    following investigator-administered cocaine in male and female mice. We applied sequential chromatin immunoprecipitation and qPCR to define\n                    <jats:italic>Nr4a1<\/jats:italic>\n                    bivalency and expression in striatum (STR), prefrontal cortex (PFC), and hippocampus (HPC). We used Pearson\u2019s correlation to quantify relationships within each brain region across treatment conditions for each sex. In female STR, cocaine increased\n                    <jats:italic>Nr4a1<\/jats:italic>\n                    mRNA while maintaining\n                    <jats:italic>Nr4a1<\/jats:italic>\n                    K4&amp;K27 bivalency. In male STR, cocaine enriched repressive H3K27me3 and K4&amp;K27 bivalency at\n                    <jats:italic>Nr4a1<\/jats:italic>\n                    and maintained\n                    <jats:italic>Nr4a1<\/jats:italic>\n                    mRNA. Furthermore, cocaine epigenetically regulated a putative NR4A1 target,\n                    <jats:italic>Cartpt<\/jats:italic>\n                    , in male PFC. This study defined the epigenetic regulation of\n                    <jats:italic>Nr4a1<\/jats:italic>\n                    in reward brain regions in male and female mice following cocaine, and, thus, shed light on the biological relevance of sex to cocaine use disorder.\n                  <\/jats:p>","DOI":"10.1038\/s41598-022-19908-9","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T06:03:06Z","timestamp":1663740186000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Cocaine regulation of Nr4a1 chromatin bivalency and mRNA in male and female mice"],"prefix":"10.1038","volume":"12","author":[{"given":"Delaney K.","family":"Fischer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keegan S.","family":"Krick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chloe","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan T.","family":"Woolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Heller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"19908_CR1","doi-asserted-by":"publisher","unstructured":"Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: Results from the 2018 National Survey on Drug Use and Health. HHS Publ. No. PEP19\u20135068, NSDUH Ser. H-54 (2018) doi:https:\/\/doi.org\/10.1016\/j.drugalcdep.2016.10.042.","DOI":"10.1016\/j.drugalcdep.2016.10.042"},{"key":"19908_CR2","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.addbeh.2010.12.002","volume":"36","author":"SJ Kasperski","year":"2011","unstructured":"Kasperski, S. J. et al. College students\u2019 use of cocaine: Results from a longitudinal study. Addict. Behav. 36, 408\u2013411 (2011).","journal-title":"Addict. Behav."},{"key":"19908_CR3","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.yfrne.2007.07.003","volume":"29","author":"JB Becker","year":"2008","unstructured":"Becker, J. B. & Hu, M. Sex differences in drug abuse. Front. Neuroendocrinol. 29, 36\u201347 (2008).","journal-title":"Front. Neuroendocrinol."},{"key":"19908_CR4","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1124\/pr.115.011163","volume":"68","author":"JB Becker","year":"2016","unstructured":"Becker, J. B. & Koob, G. F. Sex differences in animal models: Focus on addiction. Pharmacol. Rev. 68, 242\u2013263 (2016).","journal-title":"Pharmacol. Rev."},{"key":"19908_CR5","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.pbb.2008.11.002","volume":"92","author":"E Zakharova","year":"2009","unstructured":"Zakharova, E., Wade, D. & Izenwasser, S. Sensitivity to cocaine conditioned reward depends on sex and age. Pharmacol. Biochem. Behav. 92, 131\u2013134 (2009).","journal-title":"Pharmacol. Biochem. Behav."},{"key":"19908_CR6","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/S0006-8993(03)02346-1","volume":"970","author":"SJ Russo","year":"2003","unstructured":"Russo, S. J. et al. Sex differences in the conditioned rewarding effects of cocaine. Brain Res. 970, 214\u2013220 (2003).","journal-title":"Brain Res."},{"key":"19908_CR7","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s002130050979","volume":"144","author":"WJ Lynch","year":"1999","unstructured":"Lynch, W. J. & Carroll, M. E. Sex differences in the acquisition of intravenously self-administered cocaine and heroin in rats. Psychopharmacology 144, 77\u201382 (1999).","journal-title":"Psychopharmacology"},{"key":"19908_CR8","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/sj.npp.1300301","volume":"29","author":"M Hu","year":"2004","unstructured":"Hu, M., Crombag, H. S., Robinson, T. E. & Becker, J. B. Biological basis of sex differences in the propensity to self-administer cocaine. Neuropsychopharmacology 29, 81\u201385 (2004).","journal-title":"Neuropsychopharmacology"},{"key":"19908_CR9","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/s42003-021-02358-w","volume":"4","author":"AJ L\u00f3pez","year":"2021","unstructured":"L\u00f3pez, A. J. et al. Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens. Commun. Biol. 4, 883 (2021).","journal-title":"Commun. Biol."},{"key":"19908_CR10","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1111\/adb.12400","volume":"21","author":"ME Carroll","year":"2016","unstructured":"Carroll, M. E. & Lynch, W. J. How to study sex differences in addiction using animal models. Addict. Biol. 21, 1007\u20131029 (2016).","journal-title":"Addict. Biol."},{"key":"19908_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64076-5.00048-X","author":"DM Walker","year":"2018","unstructured":"Walker, D. M. & Nestler, E. J. Neuroepigenetics and addiction. Handb. Clin. Neurol. https:\/\/doi.org\/10.1016\/B978-0-444-64076-5.00048-X (2018).","journal-title":"Handb. Clin. Neurol."},{"key":"19908_CR12","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/j.biopsych.2018.04.009","volume":"84","author":"DM Walker","year":"2018","unstructured":"Walker, D. M. et al. Cocaine self-administration alters transcriptome-wide responses in the brain\u2019s reward circuitry. Biol. Psychiatry 84, 867\u2013880 (2018).","journal-title":"Biol. Psychiatry"},{"key":"19908_CR13","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1038\/s41386-018-0008-x","volume":"43","author":"RC Pierce","year":"2018","unstructured":"Pierce, R. C. et al. Environmental, genetic and epigenetic contributions to cocaine addiction. Neuropsychopharmacology 43, 1471\u20131480 (2018).","journal-title":"Neuropsychopharmacology"},{"key":"19908_CR14","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.neubiorev.2018.08.018","volume":"106","author":"D De Sa Nogueira","year":"2019","unstructured":"De Sa Nogueira, D., Merienne, K. & Befort, K. Neuroepigenetics and addictive behaviors: Where do we stand?. Neurosci. Biobehav. Rev. 106, 58\u201372 (2019).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"19908_CR15","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/nrn3111","volume":"12","author":"AJ Robison","year":"2011","unstructured":"Robison, A. J. & Nestler, E. J. Transcriptional and epigenetic mechanisms of addiction. Nat. Rev. Neurosci. 12, 623\u2013637 (2011).","journal-title":"Nat. Rev. Neurosci."},{"key":"19908_CR16","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.neuron.2019.01.016","volume":"102","author":"EJ Nestler","year":"2019","unstructured":"Nestler, E. J. & L\u00fcscher, C. The molecular basis of drug addiction: Linking epigenetic to synaptic and circuit mechanisms. Neuron 102, 48\u201359 (2019).","journal-title":"Neuron"},{"key":"19908_CR17","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.conb.2014.11.002","volume":"30","author":"DM Walker","year":"2015","unstructured":"Walker, D. M., Cates, H. M., Heller, E. A. & Nestler, E. J. Regulation of chromatin states by drugs of abuse. Curr. Opin. Neurobiol. 30, 112\u2013121 (2015).","journal-title":"Curr. Opin. Neurobiol."},{"key":"19908_CR18","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.neuron.2005.09.023","volume":"48","author":"A Kumar","year":"2005","unstructured":"Kumar, A. et al. Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron 48, 303\u2013314 (2005).","journal-title":"Neuron"},{"key":"19908_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3381","author":"SJ Russo","year":"2013","unstructured":"Russo, S. J. & Nestler, E. J. The brain reward circuitry in mood disorders. Nat. Rev. Neurosci. https:\/\/doi.org\/10.1038\/nrn3381 (2013).","journal-title":"Nat. Rev. Neurosci."},{"key":"19908_CR20","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/S2215-0366(16)00104-8","volume":"3","author":"GF Koob","year":"2016","unstructured":"Koob, G. F. & Volkow, N. D. Neurobiology of addiction: A neurocircuitry analysis. The Lancet Psychiatry 3, 760\u2013773 (2016).","journal-title":"The Lancet Psychiatry"},{"key":"19908_CR21","doi-asserted-by":"publisher","first-page":"9511","DOI":"10.1073\/pnas.1307116110","volume":"110","author":"E Jordi","year":"2013","unstructured":"Jordi, E. et al. Differential effects of cocaine on histone posttranslational modifications in identified populations of striatal neurons. Proc. Natl. Acad. Sci. 110, 9511\u20139516 (2013).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"19908_CR22","doi-asserted-by":"publisher","first-page":"6626","DOI":"10.1073\/pnas.1018514108","volume":"108","author":"Z Zhou","year":"2011","unstructured":"Zhou, Z., Yuan, Q., Mash, D. C. & Goldman, D. Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol. Proc. Natl. Acad. Sci. 108, 6626\u20136631 (2011).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"19908_CR23","doi-asserted-by":"publisher","first-page":"8305","DOI":"10.1523\/JNEUROSCI.0800-19.2019","volume":"39","author":"PA Gajewski","year":"2019","unstructured":"Gajewski, P. A. et al. Epigenetic regulation of hippocampal fosb expression controls behavioral responses to cocaine. J. Neurosci. 39, 8305\u20138314 (2019).","journal-title":"J. Neurosci."},{"key":"19908_CR24","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1007\/s12035-022-02722-9","volume":"59","author":"D De Sa Nogueira","year":"2022","unstructured":"De Sa Nogueira, D. et al. Hippocampal cannabinoid 1 receptors are modulated following cocaine self-administration in male rats. Mol. Neurobiol. 59, 1896\u20131911 (2022).","journal-title":"Mol. Neurobiol."},{"key":"19908_CR25","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.2328-10.2010","author":"G Sadri-Vakili","year":"2010","unstructured":"Sadri-Vakili, G. et al. Cocaine-induced chromatin remodeling increases brain-derived neurotrophic factor transcription in the Rat Medial prefrontal cortex, which alters the reinforcing efficacy of cocaine. J. Neurosci. https:\/\/doi.org\/10.1523\/jneurosci.2328-10.2010 (2010).","journal-title":"J. Neurosci."},{"key":"19908_CR26","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.neuropharm.2018.08.030","volume":"141","author":"YX Zhang","year":"2018","unstructured":"Zhang, Y. X. et al. The histone demethylase KDM6B in the medial prefrontal cortex epigenetically regulates cocaine reward memory. Neuropharmacology 141, 113\u2013125 (2018).","journal-title":"Neuropharmacology"},{"key":"19908_CR27","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1126\/science.1063127","volume":"293","author":"T Jenuwein","year":"2001","unstructured":"Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074\u20131080 (2001).","journal-title":"Science"},{"key":"19908_CR28","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/47412","volume":"403","author":"BD Strahl","year":"2000","unstructured":"Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41\u201345 (2000).","journal-title":"Nature"},{"key":"19908_CR29","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.brainres.2014.09.069","volume":"1628","author":"G Sadri-Vakili","year":"2015","unstructured":"Sadri-Vakili, G. Cocaine triggers epigenetic alterations in the corticostriatal circuit. Brain Res. 1628, 50\u201359 (2015).","journal-title":"Brain Res."},{"key":"19908_CR30","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.biopsych.2020.08.005","volume":"89","author":"CT Werner","year":"2021","unstructured":"Werner, C. T., Altshuler, R. D., Shaham, Y. & Li, X. Epigenetic mechanisms in drug relapse. Biol. Psychiatry 89, 331\u2013338 (2021).","journal-title":"Biol. Psychiatry"},{"key":"19908_CR31","doi-asserted-by":"publisher","first-page":"R65","DOI":"10.1186\/gb-2014-15-4-r65","volume":"15","author":"J Feng","year":"2014","unstructured":"Feng, J. et al. Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens. Genome Biol. 15, R65 (2014).","journal-title":"Genome Biol."},{"key":"19908_CR32","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.cell.2006.02.041","volume":"125","author":"BE Bernstein","year":"2006","unstructured":"Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315\u2013326 (2006).","journal-title":"Cell"},{"key":"19908_CR33","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1101\/gad.219626.113","volume":"27","author":"P Voigt","year":"2013","unstructured":"Voigt, P., Tee, W.-W. & Reinberg, D. A double take on bivalent promoters. Genes Dev. 27, 1318\u20131338 (2013).","journal-title":"Genes Dev."},{"key":"19908_CR34","doi-asserted-by":"publisher","first-page":"2170","DOI":"10.1101\/gr.275736.121","volume":"31","author":"D Kumar","year":"2021","unstructured":"Kumar, D., Cinghu, S., Oldfield, A. J., Yang, P. & Jothi, R. Decoding the function of bivalent chromatin in development and cancer. Genome Res. 31, 2170\u20132184 (2021).","journal-title":"Genome Res."},{"key":"19908_CR35","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.neuron.2017.09.020","volume":"96","author":"C Nasca","year":"2017","unstructured":"Nasca, C. et al. Role of the astroglial glutamate exchanger xCT in ventral hippocampus in resilience to stress. Neuron 96, 402\u2013413 (2017).","journal-title":"Neuron"},{"key":"19908_CR36","doi-asserted-by":"publisher","first-page":"4386","DOI":"10.1074\/jbc.M115.672931","volume":"291","author":"L Yan","year":"2016","unstructured":"Yan, L. et al. Epigenomic landscape of human fetal brain, heart, and liver. J. Biol. Chem. 291, 4386\u20134398 (2016).","journal-title":"J. Biol. Chem."},{"key":"19908_CR37","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1038\/nbt.3652","volume":"34","author":"A Weiner","year":"2016","unstructured":"Weiner, A. et al. Co-ChIP enables genome-wide mapping of histone mark co-occurrence at single-molecule resolution. Nat. Biotechnol. 34, 953\u2013961 (2016).","journal-title":"Nat. Biotechnol."},{"key":"19908_CR38","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/s41467-020-14331-y","volume":"11","author":"MD Carpenter","year":"2020","unstructured":"Carpenter, M. D. et al. Nr4a1 suppresses cocaine-induced behavior via epigenetic regulation of homeostatic target genes. Nat. Commun. 11, 504 (2020).","journal-title":"Nat. Commun."},{"key":"19908_CR39","doi-asserted-by":"publisher","first-page":"eaba4221","DOI":"10.1126\/sciadv.aba4221","volume":"6","author":"KE Savell","year":"2020","unstructured":"Savell, K. E. et al. A dopamine-induced gene expression signature regulates neuronal function and cocaine response. Sci. Adv. 6, eaba4221 (2020).","journal-title":"Sci. Adv."},{"key":"19908_CR40","doi-asserted-by":"publisher","first-page":"ENEURO.0305-19.","DOI":"10.1523\/ENEURO.0305-19.2019","volume":"6","author":"M-D Cirnaru","year":"2019","unstructured":"Cirnaru, M.-D. et al. Nuclear receptor nr4a1 regulates striatal striosome development and dopamine D 1 receptor signaling. Eneuro 6, ENEURO.0305-19.2019 (2019).","journal-title":"Eneuro"},{"key":"19908_CR41","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1007\/s00213-008-1343-0","volume":"202","author":"E Bourhis","year":"2009","unstructured":"Bourhis, E. et al. The transcription factors Nur77 and retinoid X receptors participate in amphetamine-induced locomotor activities. Psychopharmacology 202, 635\u2013648 (2009).","journal-title":"Psychopharmacology"},{"key":"19908_CR42","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1111\/j.1471-4159.2007.04494.x","volume":"102","author":"F Volpicelli","year":"2007","unstructured":"Volpicelli, F. et al. Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain neurons in vitro. J. Neurochem. 102, 441\u2013453 (2007).","journal-title":"J. Neurochem."},{"key":"19908_CR43","doi-asserted-by":"publisher","first-page":"15923","DOI":"10.1523\/JNEUROSCI.3910-09.2009","volume":"29","author":"B Kadkhodaei","year":"2009","unstructured":"Kadkhodaei, B. et al. Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons. J. Neurosci. 29, 15923\u201315932 (2009).","journal-title":"J. Neurosci."},{"key":"19908_CR44","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1038\/npp.2016.253","volume":"42","author":"MS Bridi","year":"2017","unstructured":"Bridi, M. S., Hawk, J. D., Chatterjee, S., Safe, S. & Abel, T. Pharmacological activators of the NR4A nuclear receptors enhance LTP in a CREB\/CBP-dependent manner. Neuropsychopharmacology 42, 1243\u20131253 (2017).","journal-title":"Neuropsychopharmacology"},{"key":"19908_CR45","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.jneumeth.2018.07.006","volume":"308","author":"SJ Xu","year":"2018","unstructured":"Xu, S. J. & Heller, E. A. Single sample sequencing (S3EQ) of epigenome and transcriptome in nucleus accumbens. J. Neurosci. Methods 308, 62\u201373 (2018).","journal-title":"J. Neurosci. Methods"},{"key":"19908_CR46","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/978-1-62703-080-9_22","volume-title":"Methods in Molecular Biology","author":"G-H Peng","year":"2012","unstructured":"Peng, G.-H. & Chen, S. Double chromatin immunoprecipitation: Analysis of target co-occupancy of retinal transcription factors. In Methods in Molecular Biology (eds Weber, B. H. F. & Langmann, T.) 311\u2013328 (Humana Press, 2012). https:\/\/doi.org\/10.1007\/978-1-62703-080-9_22."},{"key":"19908_CR47","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1016\/j.tibs.2010.05.006","volume":"35","author":"TK Barth","year":"2010","unstructured":"Barth, T. K. & Imhof, A. Fast signals and slow marks: The dynamics of histone modifications. Trends Biochem. Sci. 35, 618\u2013626 (2010).","journal-title":"Trends Biochem. Sci."},{"key":"19908_CR48","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.4103\/1673-5374.235029","volume":"13","author":"N Zsindely","year":"2018","unstructured":"Zsindely, N. & Bodai, L. Histone methylation in Huntington\u2019s disease: Are bivalent promoters the critical targets?. Neural Regen. Res. 13, 1191 (2018).","journal-title":"Neural Regen. Res."},{"key":"19908_CR49","doi-asserted-by":"publisher","first-page":"19809","DOI":"10.1073\/pnas.0810133105","volume":"105","author":"J Rodriguez","year":"2008","unstructured":"Rodriguez, J. et al. Bivalent domains enforce transcriptional memory of DNA methylated genes in cancer cells. Proc. Natl. Acad. Sci. 105, 19809\u201319814 (2008).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"19908_CR50","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1158\/0008-5472.CAN-17-1724","volume":"78","author":"AW Hall","year":"2018","unstructured":"Hall, A. W. et al. Bivalent chromatin domains in glioblastoma reveal a subtype-specific signature of glioma stem cells. Cancer Res. 78, 2463\u20132474 (2018).","journal-title":"Cancer Res."},{"key":"19908_CR51","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1158\/0008-5472.CAN-17-1650","volume":"78","author":"E Curry","year":"2018","unstructured":"Curry, E. et al. Genes predisposed to DNA hypermethylation during acquired resistance to chemotherapy are identified in ovarian tumors by bivalent chromatin domains at initial diagnosis. Cancer Res. 78, 1383\u20131391 (2018).","journal-title":"Cancer Res."},{"key":"19908_CR52","doi-asserted-by":"publisher","first-page":"37393","DOI":"10.1038\/srep37393","volume":"6","author":"SH Bernhart","year":"2016","unstructured":"Bernhart, S. H. et al. Changes of bivalent chromatin coincide with increased expression of developmental genes in cancer. Sci. Rep. 6, 37393 (2016).","journal-title":"Sci. Rep."},{"key":"19908_CR53","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.neuron.2007.12.019","volume":"57","author":"D Belin","year":"2008","unstructured":"Belin, D. & Everitt, B. J. Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum. Neuron 57, 432\u2013441 (2008).","journal-title":"Neuron"},{"key":"19908_CR54","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/0014-2999(89)90524-4","volume":"173","author":"JW Boja","year":"1989","unstructured":"Boja, J. W. & Kuhar, M. J. [3H]cocaine binding and inhibition of [3H]dopamine uptake is similar in both the rat striatum and nucleus accumbens. Eur. J. Pharmacol. 173, 215\u2013217 (1989).","journal-title":"Eur. J. Pharmacol."},{"key":"19908_CR55","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1097\/FBP.0000000000000099","volume":"26","author":"MMJ Veeneman","year":"2015","unstructured":"Veeneman, M. M. J., Damsteegt, R. & Vanderschuren, L. J. M. J. The nucleus accumbens shell and the dorsolateral striatum mediate the reinforcing effects of cocaine through a serial connection. Behav. Pharmacol. 26, 193\u2013199 (2015).","journal-title":"Behav. Pharmacol."},{"key":"19908_CR56","first-page":"11","volume":"17","author":"MD Carpenter","year":"2022","unstructured":"Carpenter, M. D. et al. Cell-type specific profiling of histone post-translational modifications in the adult mouse striatum. bioRxiv 17, 11 (2022).","journal-title":"bioRxiv"},{"key":"19908_CR57","doi-asserted-by":"publisher","first-page":"e16619","DOI":"10.1371\/journal.pone.0016619","volume":"6","author":"MI Davis","year":"2011","unstructured":"Davis, M. I. & Puhl, H. L. Nr4a1-eGFP is a marker of striosome-matrix architecture, development and activity in the extended striatum. PLoS ONE 6, e16619 (2011).","journal-title":"PLoS ONE"},{"key":"19908_CR58","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1038\/nn1654","volume":"9","author":"MK Lobo","year":"2006","unstructured":"Lobo, M. K., Karsten, S. L., Gray, M., Geschwind, D. H. & Yang, X. W. FACS-array profiling of striatal projection neuron subtypes in juvenile and adult mouse brains. Nat. Neurosci. 9, 443\u2013452 (2006).","journal-title":"Nat. Neurosci."},{"key":"19908_CR59","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1111\/j.1369-1600.2010.00296.x","volume":"16","author":"S Edwards","year":"2011","unstructured":"Edwards, S., Bachtell, R. K., Guzman, D., Whisler, K. N. & Self, D. W. Emergence of context-associated GluR1 and ERK phosphorylation in the nucleus accumbens core during withdrawal from cocaine self-administration. Addict. Biol. 16, 450\u2013457 (2011).","journal-title":"Addict. Biol."},{"key":"19908_CR60","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.neuropharm.2016.03.049","volume":"108","author":"AG Salinas","year":"2016","unstructured":"Salinas, A. G., Davis, M. I., Lovinger, D. M. & Mateo, Y. Dopamine dynamics and cocaine sensitivity differ between striosome and matrix compartments of the striatum. Neuropharmacology 108, 275\u2013283 (2016).","journal-title":"Neuropharmacology"},{"key":"19908_CR61","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.molcel.2013.01.038","volume":"49","author":"E Calo","year":"2013","unstructured":"Calo, E. & Wysocka, J. Modification of enhancer chromatin: What, how, and why?. Mol. Cell 49, 825\u2013837 (2013).","journal-title":"Mol. Cell"},{"key":"19908_CR62","doi-asserted-by":"publisher","first-page":"4198","DOI":"10.1038\/emboj.2011.295","volume":"30","author":"A Pekowska","year":"2011","unstructured":"Pekowska, A. et al. H3K4 tri-methylation provides an epigenetic signature of active enhancers. EMBO J. 30, 4198\u20134210 (2011).","journal-title":"EMBO J."},{"key":"19908_CR63","doi-asserted-by":"publisher","first-page":"3593","DOI":"10.1172\/JCI64145","volume":"122","author":"JD Hawk","year":"2012","unstructured":"Hawk, J. D. et al. NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors. J. Clin. Invest. 122, 3593\u20133602 (2012).","journal-title":"J. Clin. Invest."},{"key":"19908_CR64","doi-asserted-by":"publisher","first-page":"3323","DOI":"10.1038\/s41467-018-05868-0","volume":"9","author":"JL Kwapis","year":"2018","unstructured":"Kwapis, J. L. et al. Epigenetic regulation of the circadian gene Per1 contributes to age-related changes in hippocampal memory. Nat. Commun. 9, 3323 (2018).","journal-title":"Nat. Commun."},{"key":"19908_CR65","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/j.bcp.2010.04.026","volume":"80","author":"S-A Kang","year":"2010","unstructured":"Kang, S.-A. et al. Regulation of Nur77 protein turnover through acetylation and deacetylation induced by p300 and HDAC1. Biochem. Pharmacol. 80, 867\u2013873 (2010).","journal-title":"Biochem. Pharmacol."},{"key":"19908_CR66","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.cell.2012.09.002","volume":"151","author":"P Voigt","year":"2012","unstructured":"Voigt, P. et al. Asymmetrically modified nucleosomes. Cell 151, 181\u2013193 (2012).","journal-title":"Cell"},{"key":"19908_CR67","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1038\/s41467-021-21236-x","volume":"12","author":"Y Du","year":"2021","unstructured":"Du, Y. et al. Structural mechanism of bivalent histone H3K4me3K9me3 recognition by the spindlin1\/C11orf84 complex in rRNA transcription activation. Nat. Commun. 12, 949 (2021).","journal-title":"Nat. Commun."},{"key":"19908_CR68","doi-asserted-by":"publisher","first-page":"7043","DOI":"10.1007\/s00018-021-03945-0","volume":"78","author":"LE Cabrera Zapata","year":"2021","unstructured":"Cabrera Zapata, L. E. et al. X-linked histone H3K27 demethylase Kdm6a regulates sexually dimorphic differentiation of hypothalamic neurons. Cell. Mol. Life Sci. 78, 7043\u20137060 (2021).","journal-title":"Cell. Mol. Life Sci."},{"key":"19908_CR69","doi-asserted-by":"publisher","first-page":"110616","DOI":"10.1016\/j.celrep.2022.110616","volume":"39","author":"RA Phillips","year":"2022","unstructured":"Phillips, R. A. et al. An atlas of transcriptionally defined cell populations in the rat ventral tegmental area. Cell Rep. 39, 110616 (2022).","journal-title":"Cell Rep."},{"key":"19908_CR70","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1038\/s41467-019-10704-0","volume":"10","author":"I Jaric","year":"2019","unstructured":"Jaric, I., Rocks, D., Greally, J. M., Suzuki, M. & Kundakovic, M. Chromatin organization in the female mouse brain fluctuates across the oestrous cycle. Nat. Commun. 10, 2851 (2019).","journal-title":"Nat. Commun."},{"key":"19908_CR71","doi-asserted-by":"publisher","first-page":"20150113","DOI":"10.1098\/rstb.2015.0113","volume":"371","author":"AP Arnold","year":"2016","unstructured":"Arnold, A. P. et al. The importance of having two X chromosomes. Philos. Trans. R. Soc. B. Biol. Sci. 371, 20150113 (2016).","journal-title":"Philos. Trans. R. Soc. B. Biol. Sci."},{"key":"19908_CR72","doi-asserted-by":"publisher","first-page":"4736","DOI":"10.1016\/j.molcel.2021.09.019","volume":"81","author":"S Gopalan","year":"2021","unstructured":"Gopalan, S., Wang, Y., Harper, N. W., Garber, M. & Fazzio, T. G. Simultaneous profiling of multiple chromatin proteins in the same cells. Mol. Cell 81, 4736-4746.e5 (2021).","journal-title":"Mol. Cell"},{"key":"19908_CR73","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1038\/s41587-021-00869-9","volume":"39","author":"M Bartosovic","year":"2021","unstructured":"Bartosovic, M., Kabbe, M. & Castelo-Branco, G. Single-cell CUT&Tag profiles histone modifications and transcription factors in complex tissues. Nat. Biotechnol. 39, 825\u2013835 (2021).","journal-title":"Nat. Biotechnol."},{"key":"19908_CR74","doi-asserted-by":"publisher","first-page":"9901","DOI":"10.1093\/nar\/gkx578","volume":"45","author":"H O\u2019Geen","year":"2017","unstructured":"O\u2019Geen, H. et al. dCas9-based epigenome editing suggests acquisition of histone methylation is not sufficient for target gene repression. Nucleic Acids Res. 45, 9901\u20139916 (2017).","journal-title":"Nucleic Acids Res."},{"key":"19908_CR75","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1038\/nn.2886","volume":"14","author":"S Nieuwenhuis","year":"2011","unstructured":"Nieuwenhuis, S., Forstmann, B. U. & Wagenmakers, E.-J. Erroneous analyses of interactions in neuroscience: A problem of significance. Nat. Neurosci. 14, 1105\u20131107 (2011).","journal-title":"Nat. Neurosci."},{"key":"19908_CR76","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3758\/BF03193146","volume":"39","author":"F Faul","year":"2007","unstructured":"Faul, F., Erdfelder, E., Lang, A.-G. & Buchner, A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav. Res. Methods 39, 175\u2013191 (2007).","journal-title":"Behav. Res. Methods"},{"key":"19908_CR77","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method. Methods 25, 402\u2013408 (2001).","journal-title":"Methods"},{"key":"19908_CR78","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/1471-2105-7-85","volume":"7","author":"JS Yuan","year":"2006","unstructured":"Yuan, J. S., Reed, A., Chen, F. & Stewart, C. N. Statistical analysis of real-time PCR data. BMC Bioinformatics 7, 85 (2006).","journal-title":"BMC Bioinformatics"},{"key":"19908_CR79","unstructured":"H. J. Motulsky. GraphPad statistics guide. http:\/\/www.graphpad.com\/guides\/prism\/7\/statistics\/index.htm."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19908-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19908-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19908-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T06:10:47Z","timestamp":1663740647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19908-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,21]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["19908"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-19908-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.04.22.489203","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,21]]},"assertion":[{"value":"28 June 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 September 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15735"}}