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dc.contributor.authorBayraktar, Gonca
dc.contributor.authorYuanxiang, PingAn
dc.contributor.authorConfettura, Alessandro D.
dc.contributor.authorGomes, Guilherme M.
dc.contributor.authorRaza, Syed A.
dc.contributor.authorStork, Oliver
dc.contributor.authorTajima, Shoji
dc.contributor.authorSuetake, Isao
dc.contributor.authorKarpova, Anna
dc.contributor.authorYildirim, Ferah
dc.contributor.authorKreutz, Michael R.
dc.date.accessioned2021-02-09T16:32:13Z
dc.date.available2021-02-09T16:32:13Z
dc.date.issued2020-07-29
dc.date.submitted2020-02-02
dc.identifier.issn0893-133X
dc.identifier.others41386-020-0780-2
dc.identifier.other780
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/317380
dc.description.abstractAbstract: DNA methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known about how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3A1, are tightly controlled by activation of N-methyl-D-aspartate receptors (NMDAR) containing the GluN2A subunit. Interestingly, synaptic NMDARs drive degradation of the methyltransferase in a neddylation-dependent manner. Inhibition of neddylation, the conjugation of the small ubiquitin-like protein NEDD8 to lysine residues, interrupts degradation of DNMT3A1. This results in deficits in promoter methylation of activity-dependent genes, as well as synaptic plasticity and memory formation. In turn, the underlying molecular pathway is triggered by the induction of synaptic plasticity and in response to object location learning. Collectively, the data show that plasticity-relevant signals from GluN2A-containing NMDARs control activity-dependent DNA-methylation involved in memory formation.
dc.languageen
dc.publisherSpringer International Publishing
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/378
dc.subject/631/378/2584/1695
dc.subject/13/1
dc.subject/13/51
dc.subject/13/106
dc.subject/13/109
dc.subject/13/95
dc.subject/9/30
dc.subject/14/19
dc.subject/14/35
dc.subject/14/63
dc.subject/14
dc.subject/96
dc.subject/64/60
dc.subject/82/80
dc.subjectarticle
dc.titleSynaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus
dc.typeArticle
dc.date.updated2021-02-09T16:32:13Z
prism.endingPage2130
prism.issueIdentifier12
prism.publicationNameNeuropsychopharmacology
prism.startingPage2120
prism.volume45
dc.identifier.doi10.17863/CAM.64493
dcterms.dateAccepted2020-07-20
rioxxterms.versionofrecord10.1038/s41386-020-0780-2
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBayraktar, Gonca [0000-0001-5476-4346]
dc.contributor.orcidYuanxiang, PingAn [0000-0002-3746-3282]
dc.contributor.orcidGomes, Guilherme M. [0000-0001-8566-4284]
dc.contributor.orcidSuetake, Isao [0000-0002-1246-8474]
dc.contributor.orcidKreutz, Michael R. [0000-0003-0575-6950]
dc.identifier.eissn1740-634X


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)