title: A novel motif in fungal class 1 histone deacetylases is essential for growth and development of Aspergillus.
abstract: Acetylation of the N-terminal tails of core histones is an important regulatory mechanism in eukaryotic organisms. In filamentous fungi, little is known about the enzymes that modify histone tails. However, it is increasingly evident that histone deacetylases and histone acetyltransferases are critical factors for the regulation of genes involved in fungal pathogenicity, stress response, and production of secondary metabolites such as antibiotics or fungal toxins. Here, we show that depletion of RpdA, an RPD3-type histone deacetylase of Aspergillus nidulans, leads to a pronounced reduction of growth and sporulation of the fungus. We demonstrate that a so far unnoticed motif in the C terminus of fungal RpdA histone deacetylases is required for the catalytic activity of the enzyme and consequently is essential for the viability of A. nidulans. Moreover, we provide evidence that this motif is also crucial for the survival of other, if not all, filamentous fungi, including pathogens such as Aspergillus fumigatus or Cochliobolus carbonum. Thus, the extended C terminus of RpdA-type enzymes represents a promising target for fungal-specific histone deacetylase-inhibitors that may have potential as novel antifungal compounds with medical and agricultural applications.
authors: Division of Molecular Biology, Biocenter, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors: Martin
authors: M
authors: Tribus
authors: Ingo
authors: I
authors: Bauer
authors: Johannes
authors: J
authors: Galehr
authors: Gudrun
authors: G
authors: Rieser
authors: Patrick
authors: P
authors: Trojer
authors: Gerald
authors: G
authors: Brosch
authors: Peter
authors: P
authors: Loidl
authors: Hubertus
authors: H
authors: Haas
authors: Stefan
authors: S
authors: Graessle
mesh_terms: D000107:Acetylation; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001232:Aspergillus fumigatus / Q000201:enzymology; D001233:Aspergillus nidulans / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D017124:Conserved Sequence; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005838:Genotype; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
chemical_list: D005656:Fungal Proteins; D006657:Histones; D006655:Histone Deacetylases