Regulation of histone methylation on secondary metabolite production in phytopathogenic fungi

Abstract Fungal histone methylation modification (HMM) includes methylation and demethylation at the histone lysine/arginine residues, which are catalyzed by the methyltransferases (HMTs) and demethylases (HDMs) of histone, respectively. In phytopathogenic fungi, HMM plays crucial roles in the environmental stress responses, growth and development, pathogenicity, and production of secondary metabolites (SMs). One of the most important functions of fungal HMM is to regulate the gene expression responsible for the production of SMs. Most phytopathogenic fungi produce toxic SMs, commonly known as mycotoxins, which often act as pathogenic factors causing plant diseases. This mini-review focuses on HMT- and HDM-mediated regulation of HMM and its influence on SM production in phytopathogenic fungi. Six lysine residues, five in histone H3 (K4, K9, K27, K36, and K79) and one in histone H4 (K20), are methylated by specific HMTs to affect fungal secondary metabolism. Additionally, arginine methylation at histone H4R3 and lysine demethylases (KDM4 and KDM5) have been implicated in fungal secondary metabolism. Notably, methylation at H3K4, H3K36, and H3K79 typically activates this metabolic process. By contrast, methylation at H3K9, H3K27, and H4K20 suppresses the process. HMM can activate or repress biosynthetic gene cluster expression, thereby enhancing or inhibiting fungal SM production. This strategy offers novel targets for controlling mycotoxin production in phytopathogenic fungi. We also discuss the limitations and future perspectives of manipulating HMM to control SM biosynthesis in phytopathogenic fungi.