Genome-wide identification of target genes of a mating-type α-domain transcription factor reveals functions beyond sexual development

Abstract

Penicillium chrysogenum is the main industrial producer of the β-lactam antibiotic penicillin, the most commonly used drug in the treatment of bacterial infections. Recently, a functional MAT1-1 locus encoding the α-box transcription factor MAT1-1-1 was discovered to control sexual development in P.chrysogenum. As only little was known from any organism about the regulatory functions mediated by MAT1-1-1, we applied chromatin immunoprecipitation combined with next-generation sequencing (ChIP-seq) to gain new insights into the factors that influence MAT1-1-1 functions on a molecular level and its role in genome-wide transcriptional regulatory networks. Most importantly, our data provide evidence for mating-type transcription factor functions that reach far beyond their previously understood role in sexual development. These new roles include regulation of hyphal morphology, asexual development, as well as amino acid, iron, and secondary metabolism. Furthermore, in vitroDNA-protein binding studies and downstream analysis in yeast and P.chrysogenum enabled the identification of a MAT1-1-1 DNA-binding motif, which is highly conserved among euascomycetes. Our studies pave the way to a more general understanding of these master switches for development and metabolism in all fungi, and open up new options for optimization of fungal high production strains. We describe the first application of chromatin immunoprecipitation combined with next-generation sequencing analysis (ChIP-seq) for the functional characterization of the mating-type locus-encoded transcription factor MAT1-1-1 from the industrial penicillin producer Penicillium chrysogenum, leading to the identification of multiple new target genes of MAT1-1-1 and a highly specific DNA-binding motif.