HdaA, a Major Class 2 Histone Deacetylase ofAspergillus nidulans, Affects Growth under Conditions of Oxidative Stress

Abstract

ABSTRACTHistone deacetylases (HDACs) catalyze the removal of acetyl groups from the ε-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 theSaccharomyces cerevisiaeHDA1-type histone deacetylases, is a substantial contributor to total HDAC activity in the filamentous fungusAspergillus nidulans.Now we demonstrate that deletion of thehdaAgene 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 inA. nidulans. Consequently, ΔhdaAstrains 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 thehdaAmutant strains.