Regulatory Roles of Histone Modifications in Filamentous Fungal Pathogens

Abstract

Filamentous fungal pathogens have evolved diverse strategies to infect a variety of hosts including plants and insects. The dynamic infection process requires rapid and fine-tuning regulation of fungal gene expression programs in response to the changing host environment and defenses. Therefore, transcriptional reprogramming of fungal pathogens is critical for fungal development and pathogenicity. Histone post-translational modification, one of the main mechanisms of epigenetic regulation, has been shown to play an important role in the regulation of gene expressions, and is involved in, e.g., fungal development, infection-related morphogenesis, environmental stress responses, biosynthesis of secondary metabolites, and pathogenicity. This review highlights recent findings and insights into regulatory mechanisms of histone methylation and acetylation in fungal development and pathogenicity, as well as their roles in modulating pathogenic fungi–host interactions.

The histone deacetylase Cfhos2 is a key epigenetic factor regulating appressorium development and pathogenesis in apple Glomerella leaf spot fungus Colletotrichum fructicola

“…Second, deletion of Cfhos3 or Cfhda1 had no obvious effect on fungal growth, virulence, and stress tolerances, which is consistent with a recent study reporting that hos3 or hda1 gene deletion in Alternaria alternata does not affect fungal radial growth, conidiation, virulence, carbon source utilization, and stress tolerances (Ma et al 2021). Third, in accordance with our study result that Cfhos2 is pivotal for successful GLS pathogenesis in C. fructicola, Set3C/Hos2 complex is conservatively required for full virulence of various plant and human fungal pathogens (Lai et al 2022). In sum, our study results corroborate the conserved requirement of rpd3 for vegetative growth and the conserved requirement of hos2 for pathogenesis, respectively, among filamentous ascomycetes.…”

“…First, our repeated attempt to delete Cfrpd3 gene failed, indicating a lethal effect or a severe growth defect for the mutant. Such result is in accordance with the report that deletion of rpd3 in filamentous ascomycetes is either lethal (e.g., A. nidulans, A. fumigatus, Botrytis cinerea, and M. oryzae) or causes severe growth defect (e.g., B. bassiana and F. graminearum) (Lai et al 2022). Second, deletion of Cfhos3 or Cfhda1 had no obvious effect on fungal growth, virulence, and stress tolerances, which is consistent with a recent study reporting that hos3 or hda1 gene deletion in Alternaria alternata does not affect fungal radial growth, conidiation, virulence, carbon source utilization, and stress tolerances (Ma et al 2021).…”

“…(HAT) and histone deacetylase (HDAC), is one of the best-characterized machineries (Kurdistani and Grunstein 2003). HDACs function by removing acetyl residues from the ε-amino group of lysine residues in the histone N-terminal tail, which restores the positive charge on the histone (Lai et al 2022). Such positive charge generally facilitates histone-DNA binding, thereby favors chromatin condensation and transcriptional repression (Bannister and Kouzarides 2011), but in rare case leads to transcription activation as well (Wang et al 2002).…”

“…and Fusarium fujikuro, Set3C/Hos2 also regulates the biosynthesis of secondary metabolites including aflatoxin, orsellinic acid, and gibberellin (Studt et al 2013;Pidroni et al 2018;Lan et al 2019). Hos2mediated HDAC activity causes deacetylation of H4-K16 and H3-K18 (Jeon et al 2014;Lai et al 2022), with the binding and modifications mainly locating within the gene-coding regions, and correlating with changes in expression or induction kinetics of target genes (Wang et al 2002;Wirén et al 2005;Hnisz et al 2012).…”

Systematic characterization of Ustilago maydis sirtuins shows Sir2 as a modulator of pathogenic gene expression

“…As Sir2 commonly deacetylase lysine 16 in histone 4 (H4K16) ( Robyr et al, 2002 ; Suka et al, 2002 ; Vaquero et al, 2006 ; Shimizu et al, 2012 ; Cai et al, 2021 ; Zhao and Rusche, 2022 ), we checked the H4K16 acetylation level by ChIP and RT-qPCR of the genes with enriched H4 acetylation, but no differences were observed in the acetylation of this residue ( Figure 6D ). Although lysine 14 is the main target of Sir2 in histone H4, other lysine has been observed to be deacetylated by Sir2 in different fungi ( Lai et al, 2022 ). Thus, we cannot discard a different lysine residue as the histone target of Sir2 in U. maydis .…”