Histone Acetylation Dynamics Regulate Fungal Development, Pathogenicity, and Mycotoxin Biosynthesis

Histone acetylation, catalyzed by histone acetyltransferases (HATs) and reversed by histone deacetylases (HDACs), is a central epigenetic mechanism that regulates gene expression in eukaryotes. Identifying and characterizing these enzymes has rapidly advanced our understanding of this dynamic modification. In phytopathogenic fungi, HATs and HDACs modulate several cellular processes, including development, pathogenicity, and secondary metabolism. The filamentous fungus Fusarium graminearum causes Fusarium head blight, a destructive disease that reduces wheat yield and contaminates grain with the trichothecene mycotoxin deoxynivalenol (DON). Consequently, elucidating the regulatory networks that control fungal development, host colonization, and mycotoxin biosynthesis is essential for effective disease management. This review collates current knowledge on acetylation homeostasis in phytopathogenic fungi, with particular emphasis on F. graminearum, and evaluates evidence supporting a model wherein acetylation acts as a conditional regulatory hub rather than a universal transcriptional switch. Drawing on gene-deletion mutant analyses, large-scale acetylome profiling, and comparative genomics across multiple fungal species, we first cataloged the major HAT families—GNAT, MYST, CBP/p300, and TAF1—and HDAC families—Rpd3, Hos2, Hda1, and Sir2—and summarized the lysine acetylation and deacetylation sites they target, including H2BK11, H2BK16, H3K9, H3K14, H3K18, H3K23, H3K27, and H3K56. We then examine how acetylation homeostasis, defined as the dynamic balance between acetylation and deacetylation, regulates fungal morphogenesis, pathogenicity, and DON biosynthesis in F. graminearum, highlighting the functional interplay between HAT and HDAC complexes—exemplified by Gcn5 and Hos2 (Hdf1)—and their integration with cAMP–PKA and MAPK signaling cascades. We further analyzed how acetylation-dependent regulation intersected with proteasome-mediated protein stability, non-histone acetylation, and crosstalk with histone ubiquitination and methylation and assessed how acetylation responds to host-derived metabolites and microbial competitors, thereby extending its regulatory influence beyond canonical histone marks. Finally, comparative analyses across Magnaporthe oryzae, Aspergillus species, Botrytis cinerea, and Ustilago maydis reveal both conserved and species-specific roles of acetylation in pathogenicity. We conclude by advancing a refined conceptual model wherein acetylation operates not as a universal transcriptional on/off switch but as a conditional regulatory hub and is site-, locus-, and stage-specific and signal-responsive. Future studies that combine ChIP-seq, CUT&Tag, and multi-omics approaches will further clarify the direct molecular targets of HATs and HDACs and define their stage-specific activities during host colonization, thereby enabling the design of precise, pathogen-specific interventions. This framework offers new perspectives for developing targeted strategies to manage fungal diseases and reduce mycotoxin contamination.