VeA and MvlA repression of the cryptic orsellinic acid gene cluster in A spergillus nidulans involves histone 3 acetylation

A perplexing aspect of fungal secondary metabolite gene clusters is that most clusters remain ‘silent’ under common laboratory growth conditions where activation is obtained through gene manipulation or encounters with environmental signals. Few proteins have been found involved in repression of silent clusters. Through multicopy suppressor mutagenesis, we have identified a novel cluster suppressor in A spergillus nidulans , MvlA ( m odulator of v eA l oss). Genetic assessment of MvlA mutants revealed the role of both itself and VeA (but not the VeA partner LaeA ) in the suppression of the cryptic ors gene cluster producing orsellinic acid and its F 9775 derivatives. Loss of veA upregulates F9775A and F 9775 B production and this increase is reduced 4–5‐fold when an overexpression mvlA ( OE:mvlA ) allele is introduced into the Δ veA background. Previous studies have implicated a positive role for GcnE ( H3K9 acetyltransferase of the SAGA / ADA complex) in ors cluster expression and here we find expression of gcnE is upregulated in Δ veA and suppressed by OE:mvlA in the Δ veA background. H3K9 acetylation levels of ors cluster genes correlated with gcnE expression and F 9775 production in Δ veA and OE:mvlA Δ veA strains. Finally, deletion of gcnE in the Δ veA background abolishes ors cluster activation and F 9775 production. Together, this work supports a role for VeA and MvlA in modifying SAGA / ADA complex activity.