Histone deacetylases in fungi: novel members, new facts. Nucleic Acids Res

Acetylation is the most prominent modi®cation on core histones that strongly affects nuclear pro-cesses 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 identi®cation of novel HDACs from the ®lamentous 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 identi®ed 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 expres-sed 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 puri®ed HDAC activities of Aspergillus showed that all clas-sical 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