HdaA, a major class 2 histone deacetylase of Aspergillus nidulans, affects growth under conditions of oxidative stress.
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.
Tribus
Martin
M
Division of Molecular Biology, Biocenter, Innsbruck Medical University, Fritz-Pregl Strasse 3, A-6020 Innsbruck, Austria.
Galehr
Johannes
J
Trojer
Patrick
P
Brosch
Gerald
G
Loidl
Peter
P
Marx
Florentine
F
Haas
Hubertus
H
Graessle
Stefan
S
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
D005656:Fungal Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; D006655:Histone Deacetylases