Histone deacetylases in fungi: novel members, new facts.
Acetylation is the most prominent modification on core histones that strongly affects nuclear processes such as DNA replication, DNA repair and transcription. Enzymes responsible for the dynamic equilibrium of histone acetylation are histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this paper we describe the identification of novel HDACs from the filamentous fungi Aspergillus nidulans and the maize pathogen Cochliobolus carbonum. Two of the enzymes are homologs of Saccharomyces cerevisiae HOS3, an enzyme that has not been identified outside of the established yeast systems until now. One of these homologs, HosB, showed intrinsic HDAC activity and remarkable resistance against HDAC inhibitors like trichostatin A (TSA) when recombinant expressed in an Escherichia coli host system. Phylo genetic analysis revealed that HosB, together with other fungal HOS3 orthologs, is a member of a separate group within the classical HDACs. Immunological investigations with partially purified HDAC activities of Aspergillus showed that all classical enzymes are part of high molecular weight complexes and that a TSA sensitive class 2 HDAC constitutes the major part of total HDAC activity of the fungus. However, further biochemical analysis also revealed an NAD(+)-dependent activity that could be separated from the other activities by different types of chromatography and obviously represents an enzyme of the sirtuin class.
Trojer
Patrick
P
Department of Molecular Biology, University of Innsbruck, Peter-Mayr-Strasse 4b, Innsbruck, A-6020, Austria.
Brandtner
Eva M
EM
Brosch
Gerald
G
Loidl
Peter
P
Galehr
Johannes
J
Linzmaier
Roland
R
Haas
Hubertus
H
Mair
Karin
K
Tribus
Martin
M
Graessle
Stefan
S
D000595:Amino Acid Sequence; D001203:Ascomycota / Q000201:enzymology / Q000235:genetics*; D001233:Aspergillus nidulans / Q000201:enzymology / Q000235:genetics*; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D004926:Escherichia coli / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D015151:Immunoblotting; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D011233:Precipitin Tests; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D004271:DNA, Fungal; D007527:Isoenzymes; D011994:Recombinant Proteins; D006655:Histone Deacetylases