{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:09:57Z","timestamp":1792145397732,"version":"4.4.0"},"reference-count":77,"publisher":"Society for Neuroscience","issue":"13","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2015,4,1]]},"abstract":"<jats:p>\n                    Neuronal histone H3-lysine 4 methylation landscapes are defined by sharp peaks at gene promoters and other\n                    <jats:italic>cis<\/jats:italic>\n                    -regulatory sequences, but molecular and cellular phenotypes after neuron-specific deletion of H3K4 methyl-regulators remain largely unexplored. We report that neuronal ablation of the H3K4-specific methyltransferase,\n                    <jats:italic>Kmt2a\/Mixed-lineage leukemia 1<\/jats:italic>\n                    (\n                    <jats:italic>Mll1<\/jats:italic>\n                    ), in mouse postnatal forebrain and adult prefrontal cortex (PFC) is associated with increased anxiety and robust cognitive deficits without locomotor dysfunction. In contrast, only mild behavioral phenotypes were observed after ablation of the\n                    <jats:italic>Mll1<\/jats:italic>\n                    ortholog\n                    <jats:italic>Kmt2b\/Mll2<\/jats:italic>\n                    in PFC. Impaired working memory after\n                    <jats:italic>Kmt2a\/Mll1<\/jats:italic>\n                    ablation in PFC neurons was associated with loss of training-induced transient waves of\n                    <jats:italic>Arc<\/jats:italic>\n                    immediate early gene expression critical for synaptic plasticity. Medial prefrontal layer V pyramidal neurons, a major output relay of the cortex, demonstrated severely impaired synaptic facilitation and temporal summation, two forms of short-term plasticity essential for working memory. Chromatin immunoprecipitation followed by deep sequencing in\n                    <jats:italic>Mll1<\/jats:italic>\n                    -deficient cortical neurons revealed downregulated expression and loss of the transcriptional mark, trimethyl-H3K4, at &lt;50 loci, including the homeodomain transcription factor\n                    <jats:italic>Meis2<\/jats:italic>\n                    . Small RNA-mediated\n                    <jats:italic>Meis2<\/jats:italic>\n                    knockdown in PFC was associated with working memory defects similar to those elicited by\n                    <jats:italic>Mll1<\/jats:italic>\n                    deletion. Therefore, mature prefrontal neurons critically depend on maintenance of\n                    <jats:italic>Mll1<\/jats:italic>\n                    -regulated H3K4 methylation at a subset of genes with an essential role in cognition and emotion.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.3004-14.2015","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T12:52:02Z","timestamp":1427892722000},"page":"5097-5108","source":"Crossref","is-referenced-by-count":152,"title":["Neuronal Kmt2a\/Mll1 Histone Methyltransferase Is Essential for Prefrontal Synaptic Plasticity and Working Memory"],"prefix":"10.1523","volume":"35","author":[{"given":"Mira","family":"Jakovcevski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica Y.","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4971-1597","authenticated-orcid":false,"given":"Aslihan","family":"Dincer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behnam","family":"Javidfar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9190-8724","authenticated-orcid":false,"given":"Cyril J.","family":"Peter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda C.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong L.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venu","family":"Pothula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Francis","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ernst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Dong","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Schahram","family":"Akbarian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2015,4,1]]},"reference":[{"key":"2023041304161997000_35.13.5097.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.09.014"},{"key":"2023041304161997000_35.13.5097.2","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.1523\/JNEUROSCI.22-10-04153.2002","article-title":"Brain-derived neurotrophic factor is essential for opiate-induced plasticity of noradrenergic neurons","volume":"22","author":"Akbarian","year":"2002","journal-title":"J Neurosci"},{"key":"2023041304161997000_35.13.5097.3","doi-asserted-by":"publisher","DOI":"10.1101\/gr.7.10.986"},{"key":"2023041304161997000_35.13.5097.4","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu561"},{"key":"2023041304161997000_35.13.5097.5","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6654808"},{"key":"2023041304161997000_35.13.5097.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.10.032"},{"key":"2023041304161997000_35.13.5097.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.04.048"},{"key":"2023041304161997000_35.13.5097.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.11.006"},{"key":"2023041304161997000_35.13.5097.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.028"},{"key":"2023041304161997000_35.13.5097.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.12.001"},{"key":"2023041304161997000_35.13.5097.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001702107"},{"key":"2023041304161997000_35.13.5097.12","doi-asserted-by":"publisher","DOI":"10.1177\/1073858404268742"},{"key":"2023041304161997000_35.13.5097.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016071107"},{"key":"2023041304161997000_35.13.5097.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2004.09.006"},{"key":"2023041304161997000_35.13.5097.15","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.170"},{"key":"2023041304161997000_35.13.5097.16","doi-asserted-by":"publisher","DOI":"10.4161\/epi.6.9.16069"},{"key":"2023041304161997000_35.13.5097.17","doi-asserted-by":"publisher","DOI":"10.1242\/dev.102681"},{"key":"2023041304161997000_35.13.5097.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.08.017"},{"key":"2023041304161997000_35.13.5097.19","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/els017"},{"key":"2023041304161997000_35.13.5097.20","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(04)00061-9"},{"key":"2023041304161997000_35.13.5097.21","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1611-13.2013"},{"key":"2023041304161997000_35.13.5097.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.01.038"},{"key":"2023041304161997000_35.13.5097.23","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1152\/jn.1989.61.2.331","article-title":"Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex","volume":"61","author":"Funahashi","year":"1989","journal-title":"J Neurophysiol"},{"key":"2023041304161997000_35.13.5097.24","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8935-2-5"},{"key":"2023041304161997000_35.13.5097.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2011.02.012"},{"key":"2023041304161997000_35.13.5097.26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503072102"},{"key":"2023041304161997000_35.13.5097.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.042"},{"key":"2023041304161997000_35.13.5097.28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3732-09.2010"},{"key":"2023041304161997000_35.13.5097.29","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12007"},{"key":"2023041304161997000_35.13.5097.30","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1152\/jn.2000.83.5.3031","article-title":"Multiple forms of short-term plasticity at excitatory synapses in rat medial prefrontal cortex","volume":"83","author":"Hempel","year":"2000","journal-title":"J Neurophysiol"},{"key":"2023041304161997000_35.13.5097.31","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.78"},{"key":"2023041304161997000_35.13.5097.32","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.1.186-194.2003"},{"key":"2023041304161997000_35.13.5097.33","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3272-07.2007"},{"key":"2023041304161997000_35.13.5097.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.05.019"},{"key":"2023041304161997000_35.13.5097.35","doi-asserted-by":"publisher","DOI":"10.1021\/ja306028q"},{"key":"2023041304161997000_35.13.5097.36","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn647"},{"key":"2023041304161997000_35.13.5097.37","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3356-12.2013"},{"key":"2023041304161997000_35.13.5097.38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608722200"},{"key":"2023041304161997000_35.13.5097.39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2127-08.2008"},{"key":"2023041304161997000_35.13.5097.40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1013855108"},{"key":"2023041304161997000_35.13.5097.41","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01721-12"},{"key":"2023041304161997000_35.13.5097.42","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-3-r25"},{"key":"2023041304161997000_35.13.5097.43","doi-asserted-by":"publisher","DOI":"10.1159\/000297602"},{"key":"2023041304161997000_35.13.5097.44","doi-asserted-by":"publisher","DOI":"10.1038\/nature05453"},{"key":"2023041304161997000_35.13.5097.45","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12744"},{"key":"2023041304161997000_35.13.5097.46","doi-asserted-by":"publisher","DOI":"10.1042\/BST20130028"},{"key":"2023041304161997000_35.13.5097.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2014.09.003"},{"key":"2023041304161997000_35.13.5097.48","doi-asserted-by":"publisher","DOI":"10.3791\/717"},{"key":"2023041304161997000_35.13.5097.49","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.167"},{"key":"2023041304161997000_35.13.5097.50","doi-asserted-by":"crossref","first-page":"5154","DOI":"10.1523\/JNEUROSCI.16-16-05154.1996","article-title":"Neural mechanisms of visual working memory in prefrontal cortex of the macaque","volume":"16","author":"Miller","year":"1996","journal-title":"J Neurosci"},{"key":"2023041304161997000_35.13.5097.51","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi016"},{"key":"2023041304161997000_35.13.5097.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2011.10.003"},{"key":"2023041304161997000_35.13.5097.53","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2378-13.2013"},{"key":"2023041304161997000_35.13.5097.54","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr1079"},{"key":"2023041304161997000_35.13.5097.55","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0167-14.2014"},{"key":"2023041304161997000_35.13.5097.56","doi-asserted-by":"publisher","DOI":"10.1038\/nature01080"},{"key":"2023041304161997000_35.13.5097.57","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1152\/jn.1990.63.6.1401","article-title":"Effects of dopamine antagonists on neuronal activity related to a delayed response task in monkey prefrontal cortex","volume":"63","author":"Sawaguchi","year":"1990","journal-title":"J Neurophysiol"},{"key":"2023041304161997000_35.13.5097.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.01.003"},{"key":"2023041304161997000_35.13.5097.59","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.1.301"},{"key":"2023041304161997000_35.13.5097.60","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2012-13-3-r16"},{"key":"2023041304161997000_35.13.5097.61","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2013.0514"},{"key":"2023041304161997000_35.13.5097.62","doi-asserted-by":"publisher","DOI":"10.1038\/nature11243"},{"key":"2023041304161997000_35.13.5097.63","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2708"},{"key":"2023041304161997000_35.13.5097.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2008.03.019"},{"key":"2023041304161997000_35.13.5097.65","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-051710-134100"},{"key":"2023041304161997000_35.13.5097.66","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.151"},{"key":"2023041304161997000_35.13.5097.67","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21740"},{"key":"2023041304161997000_35.13.5097.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.04.043"},{"key":"2023041304161997000_35.13.5097.69","doi-asserted-by":"publisher","DOI":"10.1242\/dev.102392"},{"key":"2023041304161997000_35.13.5097.70","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3353"},{"key":"2023041304161997000_35.13.5097.71","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00924-09"},{"key":"2023041304161997000_35.13.5097.72","doi-asserted-by":"publisher","DOI":"10.1038\/nn1670"},{"key":"2023041304161997000_35.13.5097.73","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0974-09.2009"},{"key":"2023041304161997000_35.13.5097.74","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"2023041304161997000_35.13.5097.75","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2905"},{"key":"2023041304161997000_35.13.5097.76","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.12.033"},{"key":"2023041304161997000_35.13.5097.77","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.64.092501.114547"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.3004-14.2015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T18:26:14Z","timestamp":1681410374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.3004-14.2015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,1]]},"references-count":77,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2015,4,1]]},"published-print":{"date-parts":[[2015,4,1]]}},"alternative-id":["10.1523\/JNEUROSCI.3004-14.2015"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.3004-14.2015","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,1]]}}}