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Title:   Author  item
                                            SEONG, KYE-YONG - UNIVERSITY OF MINNESOTAitem
                                            PASQUALI, MATIAS - UNIVERSITY OF MINNESOTAitem
                                            ZHOU, XIAOYING - Purdue Universityitem
                                            SONG, JONGWOO - Ewha Woman'S Universityitem
                                            Broz, Karenitem
                                            McCormick, Susanitem
                                            DONG, YANHONG - University Of Minnesotaitem
                                            XU, JIN-RONG - Purdue Universityitem
                                            Kistler, Harold
  Submitted to: Molecular Microbiology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 2/19/2009
                                    Publication  Date: 2/19/2009
                                    Citation: Seong, K., Pasquali, M., Hilburn, K.L., Mccormick, S.P., Xu, J., Kistler, H.C. 2009. Global Gene Regulation by Fusarium Transcription Factors Tri6 and Tri10 Reveals Adaptations for Toxin Biosynthesis. Molecular Microbiology. 72:354-367.Interpretive Summary: Fungi are the most common organisms causing infectious disease in plants and may also contaminate harvested crops with harmful mycotoxins. The fungus Fusarium graminearum causes extensive losses on wheat and barley crops world-wide and contaminates harvested grain with a compound known as vomitoxin, whose levels in the food supply are strictly regulated.  This study demonstrates that the fungus is remarkably adapted for producing vomitoxin, not only by precisely regulating the genes unique to toxin synthesis but also by modifying gene expression in basic house-keeping functions of the cell to promote toxin accumulation.  Fungal cells thus become finely tuned “toxin factories” distinct from their non-toxin producing cousin species. However, this study also shows that alterations in the cellular factory’s toxin assembly line can drastically reduce production of vomitoxin and the amount of disease caused by the fungus.  These alterations point out potential targets for designing control strategies aimed at reducing toxin concentrations in the food supply and ameliorating the effects of the plant disease on production of grain.
                                Technical Abstract: Trichothecenes are isoprenoid mycotoxins and harmful contaminants of wheat infected with the filamentous fungus Fusarium graminearum. The expression of some fungal genes for trichothecene biosynthesis (Tri genes) are known to be under control of transcription factors encoded by the genes Tri6 and Tri10. To elucidate their genome-wide impact on gene regulation, Tri6 and Tri10 deletion mutants were constructed and used for microarray analyses with RNA isolated from infected wheat heads with the wildtype as the control. While only a total of 37 genes had expression levels altered = two-fold in the 'tri10 mutant, 208 genes were altered = two-fold the 'tri6 mutant including transcript levels for nearly all known Tri genes. Among those also reduced were genes coding for enzymes in the isoprenoid biosynthetic pathway from acetyl CoA to farnesyl pyrophosphate, the latter being the immediate molecular precursor to all trichothecenes. DNA sequences 5’ to the nine isoprenoid biosynthetic genes were significantly enriched (P = 0.0012) for the binding motif YNAGGCC, specific to the Cys2His2 zinc finger transcription factor Tri6p. Orthologous genes for these enzymes in two related Fusarium species that do not produce trichothecenes were not enriched for YNAGGCC.  To determine the effect of trichothecene metabolites on gene expression, cultures were treated with trichodiene, the first metabolite specific to the trichothecene biosynthetic pathway. A total of 153 genes were up-regulated by added trichodiene and these were significantly enriched for genes predicted to be involved in cellular transport including several potential drug efflux transporters that may allow for tolerance to the toxin. In conclusion, Tri6 and Tri10 not only regulate genes specific for trichothecene production but also all genes for enzymes involved in primary isoprenoid metabolism, which show evidence for adaptation for regulation by Tri6.


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