The Fusarium graminearum Histone Acetyltransferases Are Important for Morphogenesis, DON Biosynthesis, and Pathogenicity

Abstract

Post-translational modifications of chromatin structure by histone acetyltransferase (HATs) play a central role in the regulation of gene expression and various biological processes in eukaryotes. Although HAT genes have been studied in many fungi, few of them have been functionally characterized. In this study, we identified and characterized four putative HATs (FgGCN5, FgRTT109, FgSAS2, FgSAS3) in the plant pathogenic ascomycete Fusarium graminearum, the causal agent of Fusarium head blight of wheat and barley. We replaced the genes and all mutant strains showed reduced growth of F. graminearum. The ΔFgSAS3 and ΔFgGCN5 mutant increased sensitivity to oxidative and osmotic stresses. Additionally, ΔFgSAS3 showed reduced conidia sporulation and perithecium formation. Mutant ΔFgGCN5 was unable to generate any conidia and lost its ability to form perithecia. Our data showed also that FgSAS3 and FgGCN5 are pathogenicity factors required for infecting wheat heads as well as tomato fruits. Importantly, almost no Deoxynivalenol (DON) was produced either in ΔFgSAS3 or ΔFgGCN5 mutants, which was consistent with a significant downregulation of TRI genes expression. Furthermore, we discovered for the first time that FgSAS3 is indispensable for the acetylation of histone site H3K4, while FgGCN5 is essential for the acetylation of H3K9, H3K18, and H3K27. H3K14 can be completely acetylated when FgSAS3 and FgGCN5 were both present. The RNA-seq analyses of the two mutant strains provide insight into their functions in development and metabolism. Results from this study clarify the functional divergence of HATs in F. graminearum, and may provide novel targeted strategies to control secondary metabolite expression and infections of F. graminearum.

A Class 1 Histone Deacetylase as Major Regulator of Secondary Metabolite Production in Aspergillus nidulans

“…HosA might directly deacetylate specific lysines on histones H3 and H4, repressing transcription of the respective gene-region, as shown for instance for orsellinic acid and aspercryptin cluster genes ( Figure 6 ). Indeed, it has been demonstrated for the orsellinic acid cluster that H3K9 acetylation, mediated by the Saga/Ada complex, might trigger its activation ( Nützmann et al, 2011 ) and a recent publication reports on two HATs of the plant pathogenic fungus Fusarium graminearum required for the regulation of secondary metabolism via acetylation of several lysine residues of H3 ( Kong et al, 2018 ).…”

Dynamic network inference and association computation discover gene modules regulating virulence, mycotoxin and sexual reproduction in Fusarium graminearum

“…Genes and gene regulators such as signaling proteins and transcription factors (TFs) are interconnected in GRNs. Many studies have attempted to dissect GRNs using a reductionist approach by analyzing the gene expression profiles of Fg mutants [9][10][11]. Though conceptually valid, this approach is time-consuming and unrealistic as a method of decoding the highly complex GRNs of eukaryotic cells.…”

Protein Acetylation/Deacetylation: A Potential Strategy for Fungal Infection Control

“…All known bacterial KATs that have been discovered to date belong to the Gcn5-related N-acetyltransferase family; fewer deacetylases are encoded by prokaryotes, which means that acetylation and deacetylation processes in fungi are more complex with a higher proportion of acetylated proteins in eukaryotes ( Tables 1 , 2 ; Hentchel and Escalante-Semerena, 2015 ). KATs play a vital role in the morphogenetic hyphae growth, biofilm formation, drug resistance, and virulence ( Kong et al, 2018 ; Lin et al, 2020 ). In B. bassiana , deletion of g cn5 led to severe defects in colony growth and loss of cuticle infection ( Cai et al, 2018b ).…”

“…Hyphae have a strong ability to adhere and invade the host, making it easy to maintain their colonization and escape attacks from the host immune system, probably through the release of cell type-specific virulence factors, such as adhesins (e.g., Hwp1, Als3, Als10, Fav2, and Pga55), tissue-degrading enzymes (e.g., Sap4, Sap5, and Sap6), and antioxidant defense proteins (e.g., Sod5) ( Sudbery, 2011 ; Noble et al, 2017 ). Acetylation and deacetylation play critical regulatory roles in regulating the initiation and maintenance of hyphal development ( Garnaud et al, 2016 ; Kong et al, 2018 ; Lee et al, 2019 ). Tribus et al (2010) found that the repression of the promoter of rpdA knockdown strains resulted in distorted and hyperbranched hyphae and a tremendous loss of radial growth of fungal colonies.…”

“…In B. bassiana , the hyphal cells of Δ hos2 mutants are significantly longer than those of the wild type strains, which was concurrent with its inability to develop intact nuclei in hyphal cells ( Cai et al, 2018a ). The hyphal growth defects of four acetyltransferase mutants of F. graminearum , namely, Δ FgGCN5 , Δ FgRTT109 , Δ FgSAS2 , and Δ FgSAS3 mutants in solid medium, have also been reported ( Kong et al, 2018 ).…”