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dc.contributor.authorMolina-Serrano, D.en
dc.contributor.authorSchiza, V.en
dc.contributor.authorDemosthenous, Christisen
dc.contributor.authorStavrou, Emmanouilen
dc.contributor.authorOppelt, J.en
dc.contributor.authorKyriakou, DImitrisen
dc.contributor.authorLiu, W.en
dc.contributor.authorZisser, G.en
dc.contributor.authorBergler, H.en
dc.contributor.authorDang, W.en
dc.contributor.authorKirmizis, Antonisen
dc.date.accessioned2019-11-04T12:52:22Z
dc.date.available2019-11-04T12:52:22Z
dc.date.issued2016
dc.identifier.issn1469-221X
dc.identifier.urihttp://gnosis.library.ucy.ac.cy/handle/7/53256
dc.description.abstractChanges in histone modifications are an attractive model through which environmental signals, such as diet, could be integrated in the cell for regulating its lifespan. However, evidence linking dietary interventions with specific alterations in histone modifications that subsequently affect lifespan remains elusive. We show here that deletion of histone N-alpha-terminal acetyltransferase Nat4 and loss of its associated H4 N-terminal acetylation (N-acH4) extend yeast replicative lifespan. Notably, nat4Δ-induced longevity is epistatic to the effects of calorie restriction (CR). Consistent with this, (i) Nat4 expression is downregulated and the levels of N-acH4 within chromatin are reduced upon CR, (ii) constitutive expression of Nat4 and maintenance of N-acH4 levels reduces the extension of lifespan mediated by CR, and (iii) transcriptome analysis indicates that nat4Δ largely mimics the effects of CR, especially in the induction of stress-response genes. We further show that nicotinamidase Pnc1, which is typically upregulated under CR, is required for nat4Δ-mediated longevity. Collectively, these findings establish histone N-acH4 as a regulator of cellular lifespan that links CR to increased stress resistance and longevity. © 2016 The Authors. Published under the terms of the CC BY 4.0 licenseen
dc.sourceEMBO reportsen
dc.source.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84996555033&doi=10.15252%2fembr.201642540&partnerID=40&md5=2158fe6e3ec65031df79b28c1599debb
dc.subjectcontrolled studyen
dc.subjectpriority journalen
dc.subjectTime Factorsen
dc.subjectgeneen
dc.subjectprotein expressionen
dc.subjectunclassified drugen
dc.subjectdown regulationen
dc.subjectgene expression regulationen
dc.subjectnonhumanen
dc.subjectupregulationen
dc.subjectArticleen
dc.subjectmetabolismen
dc.subjectcell survivalen
dc.subjectgene expression profilingen
dc.subjectgeneticsen
dc.subjecttranscriptomeen
dc.subjectphysiologyen
dc.subjecttime factoren
dc.subjectDown-Regulationen
dc.subjectamino terminal sequenceen
dc.subjectgene inductionen
dc.subjectSaccharomyces cerevisiaeen
dc.subjectprotein processingen
dc.subjectepistasisen
dc.subjectProtein Processing, Post-Translationalen
dc.subjectHistonesen
dc.subjectdeficiencyen
dc.subjectTranscriptional Activationen
dc.subjectchromatinen
dc.subjectGene Expression Regulation, Fungalen
dc.subjecthistoneen
dc.subjectSaccharomyces cerevisiae Proteinsen
dc.subjectcalorie restrictionen
dc.subjectacetylationen
dc.subjecttranscription initiationen
dc.subjectacyltransferaseen
dc.subjectcaloric restrictionen
dc.subjectcellular stress responseen
dc.subjecthistone acetyltransferaseen
dc.subjectHistone Acetyltransferasesen
dc.subjecthistone H4en
dc.subjecthistone N-terminal acetylationen
dc.subjectlifespanen
dc.subjectlongevityen
dc.subjectN-Terminal Acetyltransferase Den
dc.subjectNat4en
dc.subjectnat4 geneen
dc.subjectNat4 proteinen
dc.subjectNAT4 protein, S cerevisiaeen
dc.subjectnicotinamidaseen
dc.subjectpeptide alpha n acetyltransferase Den
dc.subjectPnc1en
dc.subjectPnc1 proteinen
dc.subjectPNC1 protein, S cerevisiaeen
dc.subjectpolysomeen
dc.subjectprotein acetylationen
dc.subjectribosome DNAen
dc.subjectSaccharomyces cerevisiae proteinen
dc.titleLoss of Nat4 and its associated histone H4 N-terminal acetylation mediates calorie restriction-induced longevityen
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.15252/embr.201642540
dc.description.volume17
dc.description.startingpage1829
dc.description.endingpage1843
dc.type.uhtypeArticleen
dc.description.notes<p>Cited By :2</p>en
dc.source.abbreviationEMBO Rep.en
dc.contributor.orcidKirmizis, Antonis [0000-0002-3748-8711]


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