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Régulation épigénétique de la production de mycotoxines chez Fusarium graminearum

Abstract : Contamination of food with mycotoxins is a significant risk to human and animal health. Reports from the European Food Safety Authority indicate that nearly half of the food derived from cereals and unprocessed grains collected between 2007 and 2012 in 21 European countries were contaminated with Type B trichothecenes, or TCTB, and especially deoxynivalenol, or DON. These mycotoxins are produced by fungal phytopathogens on growing kernels, before harvest. On account of the global climate change, this situation may become increasingly serious. Therefore, preventing the production of mycotoxins is a task which brooks no delay. In Europe, DON is predominantly produced by Fusarium graminearum. Even though the sequential steps of the TCTB biosynthetic pathway are fairly well described, the molecular events involved in regulating this pathway are complex and remain, so far, widely misunderstood.Recent studies highlighted post-translational modifications of canonical histones as well as their variants as critical players in the regulation of mycotoxin and other secondary metabolite biosyntheses in filamentous fungi, by altering chromatin structure. In F. graminearum, it was shown that the histone deacetylase HDF1 could be involved in the activation of DON production. In contrast, H3K27me3 histone mark represses 14 % of its genome, including genes involved in secondary metabolic pathways. Histone variant H2A.Z is ubiquitous in eukaryotes and is involved in a diverse range of biological processes, including genome stability, DNA repair, transcriptional regulation and telomere silencing. However, the underlying mechanisms of these functions remain unclear. In some species, the function of H2A.Z appears to be essential. Up to now, the only one study targeted directly on the function of H2A.Z in filamentous fungi was carried out on Neurospora crassa, and identifying a role in oxidative stress response.Here, we hypothesized that H2A.Z may be involved in important biological processes of F. graminearum including those involved in the production of secondary metabolism. Therefore, this project aims to characterize the roles played by the histone variant H2A.Z in controlling development, metabolism and virulence in F. graminearum.Using a reverse genetics approach, we created six H2A.Z deleted mutants in three different F. graminearum strains. All mutants exhibit deficiency in sporulation, germination, radial growth and DON production; however, intensities in the observed effects depend on the considered genetic background. Additionally, adding back wild-type H2A.Z could not rescue mutant phenotypes. Whole-genome sequencing showed that, although H2A.Z has been totally removed from the genome, compensatory mutations occur at other sites in each mutant regardless of the genetic background, in genes involved in chromatin remodeling. Strikingly, one extra mutation was detected in the H2A.Z add-back mutants. H2A.Z overexpressed mutants have also been constructed, but no significant difference in phenotype can be observed with wild type. Considering our results as a whole, we draw the conclusion that H2A.Z is essential in F. graminearum. It is the occurrence of compensatory mutations that rescued part of the lethality caused by H2A.Z deletion. We hypothesize that profound reorganizations of gene networks allow such plasticity, with certain consequences in terms of evolution and adaptation.
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Submitted on : Monday, July 6, 2020 - 10:39:11 AM
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Zhenhui Chen. Régulation épigénétique de la production de mycotoxines chez Fusarium graminearum. Ingénierie des aliments. Université de Bordeaux, 2019. Français. ⟨NNT : 2019BORD0600⟩. ⟨tel-02890180⟩



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