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dc.contributor.authorSchiza, V.en
dc.contributor.authorMolina-Serrano, D.en
dc.contributor.authorKyriakou, DImitrisen
dc.contributor.authorHadjiantoniou, A.en
dc.contributor.authorKirmizis, Antonisen
dc.date.accessioned2019-11-04T12:52:38Z
dc.date.available2019-11-04T12:52:38Z
dc.date.issued2013
dc.identifier.issn1553-7390
dc.identifier.urihttp://gnosis.library.ucy.ac.cy/handle/7/53372
dc.description.abstractPost-translational modifications of histones play a key role in DNA-based processes, like transcription, by modulating chromatin structure. N-terminal acetylation is unique among the numerous histone modifications because it is deposited on the N-alpha amino group of the first residue instead of the side-chain of amino acids. The function of this modification and its interplay with other internal histone marks has not been previously addressed. Here, we identified N-terminal acetylation of H4 (N-acH4) as a novel regulator of arginine methylation and chromatin silencing in Saccharomyces cerevisiae. Lack of the H4 N-alpha acetyltransferase (Nat4) activity results specifically in increased deposition of asymmetric dimethylation of histone H4 arginine 3 (H4R3me2a) and in enhanced ribosomal-DNA silencing. Consistent with this, H4 N-terminal acetylation impairs the activity of the Hmt1 methyltransferase towards H4R3 in vitro. Furthermore, combinatorial loss of N-acH4 with internal histone acetylation at lysines 5, 8 and 12 has a synergistic induction of H4R3me2a deposition and rDNA silencing that leads to a severe growth defect. This defect is completely rescued by mutating arginine 3 to lysine (H4R3K), suggesting that abnormal deposition of a single histone modification, H4R3me2a, can impact on cell growth. Notably, the cross-talk between N-acH4 and H4R3me2a, which regulates rDNA silencing, is induced under calorie restriction conditions. Collectively, these findings unveil a molecular and biological function for H4 N-terminal acetylation, identify its interplay with internal histone modifications, and provide general mechanistic implications for N-alpha-terminal acetylation, one of the most common protein modifications in eukaryotes. © 2013 Schiza et al.en
dc.sourcePLoS Geneticsen
dc.source.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84884694093&doi=10.1371%2fjournal.pgen.1003805&partnerID=40&md5=1bd9b51b17597c8c0f4f485be7521f72
dc.subjectarticleen
dc.subjectunclassified drugen
dc.subjectnonhumanen
dc.subjectMutationen
dc.subjectcell growthen
dc.subjectenzyme activityen
dc.subjectgene silencingen
dc.subjectgrowth disorderen
dc.subjectarginineen
dc.subjectprotein interactionen
dc.subjectamino terminal sequenceen
dc.subjectSaccharomyces cerevisiaeen
dc.subjectamino acid substitutionen
dc.subjectenzyme inductionen
dc.subjectProtein Processing, Post-Translationalen
dc.subjectHistonesen
dc.subjectlysineen
dc.subjectmethylationen
dc.subjectchromatinen
dc.subjectSubstrate Specificityen
dc.subjecthistone modificationen
dc.subjectcaloric restrictionen
dc.subjecthistone acetyltransferaseen
dc.subjecthistone H4en
dc.subjectribosome DNAen
dc.subjectAcetylationen
dc.subjectAcetyltransferasesen
dc.subjectarginine methylationen
dc.subjectDNA, Ribosomalen
dc.subjectenzyme metabolismen
dc.subjectfungus growthen
dc.subjecthistone acetylationen
dc.subjectHmt1 methyltransferaseen
dc.subjectNat4 acetyltransferaseen
dc.titleN-alpha-terminal Acetylation of Histone H4 Regulates Arginine Methylation and Ribosomal DNA Silencingen
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1371/journal.pgen.1003805
dc.description.volume9
dc.type.uhtypeArticleen
dc.description.notes<p>Cited By :18</p>en
dc.source.abbreviationPLoS Genet.en
dc.contributor.orcidKirmizis, Antonis [0000-0002-3748-8711]


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