When the fungal pathogen Gibberella moniliformis (anamorph, Fusarium verticillioides) colonizes maize and maize-based products, it produces class B fumonisin (FB) mycotoxins, which are a significant threat to human and animal health. FB biosynthetic enzymes and accessory proteins are encoded by a set of clustered and cotranscribed genes collectively named FUM, whose molecular regulation is beginning to be unraveled by researchers. FB accumulation correlates with the amount of transcripts from the key FUM genes, FUM1, FUM21, and FUM8. In fungi in general, gene expression is often partially controlled at the chromatin level in secondary metabolism; when this is the case, the deacetylation and acetylation (and other posttranslational modifications) of histones are usually crucial in the regulation of transcription. To assess whether epigenetic factors regulate the FB pathway, we monitored FB production and FUM1, FUM21, and FUM8 expression in the presence of a histone deacetylase inhibitor and verified by chromatin immunoprecipitation the relative degree of histone acetylation in the promoter regions of FUM1, FUM21, and FUM8 under FB-inducing and noninducing conditions. Moreover, we generated transgenic F. verticillioides strains expressing GFP under the control of the FUM1 promoter to determine whether its strength under FB-inducing and noninducing conditions was influenced by its location in the genome. Our results indicate a clear and differential role for chromatin remodeling in the regulation of FUM genes. This epigenetic regulation can be attained through the modulation of histone acetylation at the level of the promoter regions of the key biosynthetic genes FUM1 and FUM21, but less so for FUM8.F umonisins are a family of mycotoxins produced by the secondary metabolism (SM) of Fusarium verticillioides (teleomorph, Gibberella moniliformis) and Fusarium proliferatum that contaminate maize and maize-based products. Within the B series of these toxins (FB), FB1, FB2, and FB3 are the ones most frequently found under field conditions and have been linked to various animal and human mycotoxicoses (23). FB are polyketides consisting of a linear 19-or 20-carbon backbone with hydroxyl, methyl, and tricarballylic acid moieties at various positions along the base chain (19). In filamentous Ascomycetes, genes involved in the biosynthesis of toxins (such as aflatoxins and trichothecenes) and of other secondary metabolites are frequently organized into clusters (6). Clustering is not observed for most biosynthetic genes in the SM of higher eukaryotes, with a few exceptions in plants (7,21). In organisms like filamentous fungi, such clustering occurs and is maintained probably because it facilitates horizontal transfer and coordinated transcriptional regulation of the genes therein (29).The FB biosynthetic gene cluster consists of 17 transcriptionally coregulated genes designated FUM1 through FUM3 and FUM6 through FUM21 (with FUM2 and FUM3 later found to be the same as FUM12 and FUM9, respectively) (1,5,18,26). While the func...

Fumonisins, toxic secondary metabolites produced by some Fusarium spp. and Aspergillus niger, have strong agro-economic and health impacts. The genes needed for their biosynthesis, named FUM, are clustered and co-expressed in fumonisin producers. In eukaryotes, coordination of transcription can be attained through shared transcription factors, whose specificity relies on the recognition of cis-regulatory elements on target promoters. A bioinformatic analysis on FUM promoters in the maize pathogens Fusarium verticillioides and Aspergillus niger identified a degenerated, over-represented motif potentially involved in the cis-regulation of FUM genes, and of fumonisin biosynthesis. The same motif was not found in various FUM homologues of fungi that do not produce fumonisins. Comparison of the transcriptional strength of the intact FUM1 promoter with a synthetic version, where the motif had been mutated, was carried out in vivo and in planta for F. verticillioides. The results showed that the motif is important for efficient transcription of the FUM1 gene.