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dc.contributor.authorZhang, Feiran
dc.contributor.authorJin, Peng
dc.contributor.authorNott, Alexander
dc.contributor.authorCheng, Jemmie
dc.contributor.authorGao, Fan
dc.contributor.authorLin, Yuan-Ta
dc.contributor.authorGjoneska, Elizabeta
dc.contributor.authorKo, Tak
dc.contributor.authorMinhas, Paras S
dc.contributor.authorZamudio Montes de Oca, Alicia
dc.contributor.authorMeng, Jia
dc.contributor.authorTsai, Li-Huei
dc.date.accessioned2017-12-11T15:39:19Z
dc.date.available2017-12-11T15:39:19Z
dc.date.issued2016-07
dc.date.submitted2016-04
dc.identifier.issn1097-6256
dc.identifier.issn1546-1726
dc.identifier.urihttp://hdl.handle.net/1721.1/112683
dc.description.abstractMutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT). The RTT missense MECP2 R306C mutation prevents MeCP2 from interacting with the NCoR/histone deacetylase 3 (HDAC3) complex; however, the neuronal function of HDAC3 is incompletely understood. We found that neuronal deletion of Hdac3 in mice elicited abnormal locomotor coordination, sociability and cognition. Transcriptional and chromatin profiling revealed that HDAC3 positively regulated a subset of genes and was recruited to active gene promoters via MeCP2. HDAC3-associated promoters were enriched for the FOXO transcription factors, and FOXO acetylation was elevated in Hdac3 knockout (KO) and Mecp2 KO neurons. Human RTT-patient-derived MECP2 R306C neural progenitor cells had deficits in HDAC3 and FOXO recruitment and gene expression. Gene editing of MECP2 R306C cells to generate isogenic controls rescued HDAC3-FOXO-mediated impairments in gene expression. Our data suggest that HDAC3 interaction with MeCP2 positively regulates a subset of neuronal genes through FOXO deacetylation, and disruption of HDAC3 contributes to cognitive and social impairment.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant NS78839)en_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/NN.4347en_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.sourcePMCen_US
dc.titleHistone deacetylase 3 associates with MeCP2 to regulate FOXO and social behavioren_US
dc.typeArticleen_US
dc.identifier.citationNott, Alexi et al. “Histone Deacetylase 3 Associates with MeCP2 to Regulate FOXO and Social Behavior.” Nature Neuroscience 19, 11 (July 2016): 1497–1505 © Nature America, Inc, part of Springer Natureen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.contributor.mitauthorNott, Alexander
dc.contributor.mitauthorCheng, Jemmie
dc.contributor.mitauthorGao, Fan
dc.contributor.mitauthorLin, Yuan-Ta
dc.contributor.mitauthorGjoneska, Elizabeta
dc.contributor.mitauthorKo, Tak
dc.contributor.mitauthorMinhas, Paras S
dc.contributor.mitauthorZamudio Montes de Oca, Alicia
dc.contributor.mitauthorMeng, Jia
dc.contributor.mitauthorTsai, Li-Huei
dc.relation.journalNature Neuroscienceen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2017-12-11T13:47:08Z
dspace.orderedauthorsNott, Alexi; Cheng, Jemmie; Gao, Fan; Lin, Yuan-Ta; Gjoneska, Elizabeta; Ko, Tak; Minhas, Paras; Zamudio, Alicia Viridiana; Meng, Jia; Zhang, Feiran; Jin, Peng; Tsai, Li-Hueien_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-2029-7193
dc.identifier.orcidhttps://orcid.org/0000-0003-4000-8827
dc.identifier.orcidhttps://orcid.org/0000-0002-2461-1135
dc.identifier.orcidhttps://orcid.org/0000-0002-3255-4740
dc.identifier.orcidhttps://orcid.org/0000-0001-6263-2423
dc.identifier.orcidhttps://orcid.org/0000-0003-1262-0592
mit.licensePUBLISHER_POLICYen_US


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