Adaptation of the Efg1p morphogenetic pathway in Candida albicans by negative autoregulation and PKA-dependent repression of the EFG1 gene.

The Efg1p regulator protein permits hyphal morphogenesis in the human fungal pathogen Candida albicans. We have identified the major promoter of the EFG1 gene as a direct target of Efg1p, resulting in negative autoregulation of EFG1. Enhanced activity of protein kinase A (PKA) isoforms Tpk1p and Tpk2p or exogenous overexpression of EFG1 led to Efg1p-dependent down-regulation of the endogenous EFG1 promoter. Serial deletion analyses of the promoter region revealed that the TATA box region was required for EFG1 autoregulation. By chromatin immunoprecipitation we detected binding of Efg1p to the EFG1 transcriptional initiation region. Furthermore, Sin3p, a component of a specific histone deacetylase complex, was shown to bind to the EFG1 promoter. sin3 mutants grew as budding pseudohyphae and were unable to form true hyphae, similar to strains constitutively expressing EFG1. We propose that the PKA signalling pathway, in addition to its importance in the initial steps of filament formation, is part of a feedback loop that controls EFG1 expression allowing continued hypha formation in inducing conditions. This autoregulation of EFG1 expression is probably mediated through the Sin3p-containing histone deacetylation complex.