title: HdaA, a major class 2 histone deacetylase of Aspergillus nidulans, affects growth under conditions of oxidative stress.
abstract: Histone deacetylases (HDACs) catalyze the removal of acetyl groups from the epsilon-amino group of distinct lysine residues in the amino-terminal tail of core histones. Since the acetylation status of core histones plays a crucial role in fundamental processes in eukaryotic organisms, such as replication and regulation of transcription, recent research has focused on the enzymes responsible for the acetylation/deacetylation of core histones. Very recently, we showed that HdaA, a member of the Saccharomyces cerevisiae HDA1-type histone deacetylases, is a substantial contributor to total HDAC activity in the filamentous fungus Aspergillus nidulans. Now we demonstrate that deletion of the hdaA gene indeed results in the loss of the main activity peak and in a dramatic reduction of total HDAC activity. In contrast to its orthologs in yeast and higher eukaryotes, HdaA has strong intrinsic activity as a protein monomer when expressed as a recombinant protein in a prokaryotic expression system. In vivo, HdaA is involved in the regulation of enzymes which are of vital importance for the cellular antioxidant response in A. nidulans. Consequently, deltahdaA strains exhibit significantly reduced growth on substrates whose catabolism generates molecules responsible for oxidative stress conditions in the fungus. Our analysis revealed that reduced expression of the fungal catalase CatB is jointly responsible for the significant growth reduction of the hdaA mutant strains.
authors.affiliation: Division of Molecular Biology, Biocenter, Innsbruck Medical University, Fritz-Pregl Strasse 3, A-6020 Innsbruck, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Tribus
authors.forename: Johannes
authors.initials: J
authors.lastname: Galehr
authors.forename: Patrick
authors.initials: P
authors.lastname: Trojer
authors.forename: Gerald
authors.initials: G
authors.lastname: Brosch
authors.forename: Peter
authors.initials: P
authors.lastname: Loidl
authors.forename: Florentine
authors.initials: F
authors.lastname: Marx
authors.forename: Hubertus
authors.initials: H
authors.lastname: Haas
authors.forename: Stefan
authors.initials: S
authors.lastname: Graessle
mesh_terms: D001233:Aspergillus nidulans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D002374:Catalase / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D025301:Hyphae / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; D006655:Histone Deacetylases