The epigenetic regulator Set9 harmonizes fungal development, secondary metabolism, and colonization capacity of...

Area of Science:

• Mycology
• Epigenetics
• Molecular Biology

Background:

• Aspergillus flavus is a food-borne pathogen producing toxic aflatoxins.
• The regulatory mechanisms of fungal virulence and toxigenesis are complex and not fully understood.
• The function of Set9, a histone methyltransferase, in A. flavus remains uncharacterized.

Purpose of the Study:

• To investigate the bio-function of Set9 in Aspergillus flavus.
• To elucidate the epigenetic regulation of fungal growth, reproduction, mycotoxin production, and pathogenicity.
• To identify potential targets for controlling A. flavus contamination.

Main Methods:

• Genetic engineering (gene deletion, domain deletion, point mutation)
• Histone methylation analysis (H4K20me2 and H4K20me3)
• RNA-sequencing (RNA-seq)
• Fungal stress response assays (oxidative and cell wall integrity)

Main Results:

• Set9 catalyzes H4K20me2 and H4K20me3, impacting fungal growth, reproduction, and mycotoxin production.
• Set9 regulates fungal colonization by modulating responses to oxidative and cell wall stress.
• The SET domain, particularly the D200 site, is crucial for Set9's methyltransferase activity.
• Set9 regulates the aflatoxin gene cluster via an AflR-like protein (ALP), distinct from AflR.

Conclusions:

• Set9 is an epigenetic regulator of Aspergillus flavus morphogenesis, secondary metabolism, and pathogenicity.
• H4K20 methylation by Set9 is a key mechanism controlling fungal virulence and aflatoxin biosynthesis.
• Set9 represents a potential novel target for managing A. flavus infections and aflatoxin contamination.