title: The histone acetyltransferase GCN5 modulates the retrograde response and genome stability determining yeast longevity.
abstract: Transcriptional silencing decreases at both subtelomeric and silent mating-type loci and increases at the ribosomal DNA locus during the replicative life span of the yeast Saccharomyces cerevisiae . Evidence exists that epigenetic changes in the regulatory state of chromatin may be a causal factor in determining yeast longevity and that histone deacetylases play a role. The significance of histone acetylation has been examined here in more detail. Deletion of the histone acetyltransferase gene GCN5 suppressed the extension of replicative life span afforded by the induction of the retrograde response, which signals mitochondrial dysfunction and leads to changes in nuclear gene expression. It was difficult to ascribe this effect to changes in transcriptional silencing in any of the three known types of heterochromatin. However, a promoter related effect was uncovered by the participation of GCN5 in the induction of the retrograde response. Gcn5p and the retrograde signal transducer Rtg2p are components of the histone acetyltransferase coactivator complex SLIK. Rtg2p blocks the production of extrachromosomal ribosomal DNA circles when it is not engaged in transmission of the retrograde signal. Deletion of GCN5 , which disrupts the integrity of SLIK, suppressed circle accumulation. The results indicate that Gcn5p and SLIK impact the interplay between the retrograde response signal and Rtg2p with consequences for the induction of the response and circle production. Rtg2p and Gcn5p in the SLIK complex link metabolism to stress responses, chromatin-dependent gene regulation, and genome stability in yeast aging.
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Kim
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ohkuni
authors.forename: Elodie
authors.initials: E
authors.lastname: Couplan
authors.forename: S Michal
authors.initials: SM
authors.lastname: Jazwinski
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D020868:Gene Silencing; D016681:Genome, Fungal; D051548:Histone Acetyltransferases; D011494:Protein Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D000099224:p300-CBP-Associated Factor
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D011494:Protein Kinases; D029701:Saccharomyces cerevisiae Proteins; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor