HapX-mediated H2B deub1 and SreA-mediated H2A.Z deposition coordinate in fungal iron homeostasis during infection

Plant pathogens are challenged by host-derived iron starvation or excess during infection, but it is unclear how pathogens counteract the iron stress. Here, we found that Fusarium graminearum suffers from iron excess during the colonization of wheat heads. Iron-responsive transcription factors FgHapX and FgSreA regulate both the sensitivity to iron excess and virulence. Further, FgHapX derepresses iron utilization genes and FgSREA via dissociating from their promoters and activates iron storage gene via promoting histone H2B deubiquitination (H2B deub1) at its promoter under iron excess treatment, which is dependent on the CCAAT-binding complex (CBC). Meantime, FgSreA inhibits iron acquisition genes via facilitating the deposition of histone variant H2A.Z and histone 3 lysine 27 trimethylation (H3K27 me3) at the first nucleosome after transcription start site (+1 nucleosome) upon iron excess. In addition, monothiol glutaredoxin FgGrx4 is responsible for iron excess-sensing and controls the transcription activity of FgHapX and FgSreA via modulating their enrichment at target genes or recruitment of epigenetic elements. Taken together, our finding reveals the molecular mechanisms of adapting iron excess mediated by FgHapX and FgSreA during infection in F. graminearum, which will provide a novel insight into epigenetic regulation in iron homeostasis in eukaryotes.