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dc.contributor.authorGuan, Ji-Song
dc.contributor.authorGiacometti, Emanuela
dc.contributor.authorDannenberg, Jan-Hermen
dc.contributor.authorJoseph, Nadine
dc.contributor.authorGao, Jun
dc.contributor.authorDePinho, Ronald A.
dc.contributor.authorJaenisch, Rudolf
dc.contributor.authorTsai, Li-Huei
dc.contributor.authorHaggarty, Stephen John
dc.contributor.authorNieland, Thomas
dc.contributor.authorZhou, Ying
dc.contributor.authorWang, Xinyu
dc.contributor.authorMazitschek, Ralph
dc.contributor.authorBradner, James Elliott
dc.date.accessioned2013-04-29T13:38:21Z
dc.date.issued2012
dc.identifier.citationGuan, Ji-Song, Stephen John Haggarty, Emanuela Giacometti, Jan-Hermen Dannenberg, Nadine Joseph, Jun Gao, Thomas Nieland, et al. 2012. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459(7243): 55-60.en_US
dc.identifier.issn0028-0836en_US
dc.identifier.issn1476-4687en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10590437
dc.description.abstractChromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACis requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not that of HDAC1, decreased dendritic spine density, synapse number, synaptic plasticity and memory formation. Conversely, Hdac2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic treatment with HDACis in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic treatment with HDACis. Correspondingly, treatment with HDACis failed to further facilitate memory formation in Hdac2-deficient mice. Furthermore, analysis of promoter occupancy revealed an association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Taken together, our results suggest that HDAC2 functions in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment.en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofdoi:10.1038/nature07925en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498958/pdf/en_US
dash.licenseLAA
dc.titleHDAC2 Negatively Regulates Memory Formation and Synaptic Plasticityen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalNatureen_US
dash.depositing.authorHaggarty, Stephen John
dc.date.available2013-04-29T13:38:21Z
dc.identifier.doi10.1038/nature07925*
dash.authorsorderedfalse
dash.contributor.affiliatedNieland, Thomas
dash.contributor.affiliatedMazitschek, Ralph
dash.contributor.affiliatedHaggarty, Stephen
dash.contributor.affiliatedBradner, James E


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