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dc.contributor.authorHeiman, Myriam
dc.contributor.authorJordi, Emmanuelle
dc.contributor.authorMarion-Poll, Lucile
dc.contributor.authorGuermonprez, Pierre
dc.contributor.authorCheng, Shuk Kei
dc.contributor.authorNairn, Angus C.
dc.contributor.authorGreengard, Paul
dc.contributor.authorGirault, Jean-Antoine
dc.date.accessioned2014-03-24T15:49:56Z
dc.date.available2014-03-24T15:49:56Z
dc.date.issued2013-05
dc.date.submitted2013-03
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/85903
dc.description.abstractDrugs of abuse, such as cocaine, induce changes in gene expression and epigenetic marks including alterations in histone posttranslational modifications in striatal neurons. These changes are thought to participate in physiological memory mechanisms and to be critical for long-term behavioral alterations. However, the striatum is composed of multiple cell types, including two distinct populations of medium-sized spiny neurons, and little is known concerning the cell-type specificity of epigenetic modifications. To address this question we used bacterial artificial chromosome transgenic mice, which express EGFP fused to the N-terminus of the large subunit ribosomal protein L10a driven by the D1 or D2 dopamine receptor (D1R, D2R) promoter, respectively. Fluorescence in nucleoli was used to sort nuclei from D1R- or D2R-expressing neurons and to quantify by flow cytometry the cocaine-induced changes in histone acetylation and methylation specifically in these two types of nuclei. The two populations of medium-sized spiny neurons displayed different patterns of histone modifications 15 min or 24 h after a single injection of cocaine or 24 h after seven daily injections. In particular, acetylation of histone 3 on Lys 14 and of histone 4 on Lys 5 and 12, and methylation of histone 3 on Lys 9 exhibited distinct and persistent changes in the two cell types. Our data provide insights into the differential epigenetic responses to cocaine in D1R- and D2R-positive neurons and their potential regulation, which may participate in the persistent effects of cocaine in these neurons. The method described should have general utility for studying nuclear modifications in different types of neuronal or nonneuronal cell types.en_US
dc.description.sponsorshipJPB Foundationen_US
dc.language.isoen_US
dc.publisherNational Academy of Sciences (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1307116110en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePNASen_US
dc.titleDifferential effects of cocaine on histone posttranslational modifications in identified populations of striatal neuronsen_US
dc.typeArticleen_US
dc.identifier.citationJordi, E., M. Heiman, L. Marion-Poll, P. Guermonprez, S. K. Cheng, A. C. Nairn, P. Greengard, and J.-A. Girault. “Differential Effects of Cocaine on Histone Posttranslational Modifications in Identified Populations of Striatal Neurons.” Proceedings of the National Academy of Sciences 110, no. 23 (June 4, 2013): 9511–9516.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.mitauthorHeiman, Myriamen_US
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsJordi, E.; Heiman, M.; Marion-Poll, L.; Guermonprez, P.; Cheng, S. K.; Nairn, A. C.; Greengard, P.; Girault, J.-A.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-6365-8673
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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