Fusaria are among the most important group of phytopathogenic fungi infecting various economically important host plants worldwide. Besides enormous crop losses caused by these fungal attacks, fusaria are able to produce a diverse spectrum of natural compounds, referred to as secondary metabolites. These compounds include mycotoxins that frequently contaminate food and feed, thereby posing a serious health threat to animals and humans when consumed. A crucial step towards the development of efficient and durable strategies against fungal infections and contaminations with mycotoxins is to understand the regulatory network that orchestrates pathogenesis and secondary metabolite biosynthesis. Gene expression in eukaryotes functions within the context of chromatin. This includes histone posttranslational modifications that do not alter the DNA sequence, but affect the read out thereof, i.e. inducing or silencing expression of the underlying genes. These histone marks emerge more and more as key factors in regulating fungal virulence and secondary metabolism. Our working hypothesis is that during fungal development and during infection of the plant, the chromatin structure is dynamic and driven by changes in the histone marks deposited on the genome. These changes allow the expression of virulence- and secondary metabolite-related genes hitherto silent as optionally embedded in repressive chromatin. Among known eukaryotic histone marks, although regularly found as decorating transcriptionally active genes, the role of the variant H2A.Z remains to date a riddle, with conflictual roles often described for the same organisms. The function of H2A.Z in fungi has, to date, received very little attention. HISTOVAR proposes to focus on the chromatin dynamics in the two prominent Fusarium spp., Fusarium fujikuroi and Fusarium graminearum, infecting rice and wheat, respectively, and to study the role of so far overlooked – but likely essential – mechanisms involving H2A.Z during secondary metabolism and pathogenesis. HISTOVAR is a collaborative project between an Austrian and a French research group who both aim at, ultimately, finding the Fusarium’s “Achilles’ heel” that could serve as preferential target(s) for efficient, durable, and environment-friendly fighting strategies against fungal infections and mycotoxin contamination. By a combination of reverse genetics and whole genome approaches (transcriptome, metabolome and epigenome analyses), HISTOVAR will provide groundbreaking knowledge regarding the function of H2A.Z in fungal development, pathogenicity, and secondary metabolism.