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 Aspergillus nidulans, MvlA (modulator of veA loss). 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 F9775 derivatives. Loss of veA upregulates F9775A and F9775B production and this increase is reduced 4-5-fold when an overexpression mvlA (OE: mvlA) allele is introduced into the Delta 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 Delta veA and suppressed by OE: mvlA in the Delta veA background. H3K9 acetylation levels of ors cluster genes correlated with gcnE expression and F9775 production in Delta veA and OE:mvlA Delta veA strains. Finally, deletion of gcnE in the Delta veA background abolishes ors cluster activation and F9775 production. Together, this work supports a role for VeA and MvlA in modifying SAGA/ADA complex activity.
