Genome-Wide Mapping Reveals an Extensive AtfA Regulatory Influence on Development, Metabolism, and Stress...

Asexual sporulation (conidiogenesis) in filamentous fungi is a complex developmental process that requires precise coordination with primary metabolism and environmental stress responses. In the model fungus Aspergillus nidulans, we demonstrate that the bZIP-type transcription factor AtfA plays a central role in integrating conidiogenesis with the underlying metabolic and regulatory networks. Using combined ChIP-seq and RNA-seq analyses in wild-type, ∆atfA, and atfA-complemented strains under stress-free and oxidative stress (menadione) conditions, we identify a conserved AtfA binding motif and map its functional targets genome-wide. Our data reveal that AtfA binding to its target promoters is largely stress-independent, suggesting a preemptive regulatory mechanism in conidial development. AtfA directly binds to the promoters of genes involved in the MAPK signaling cascade, light-dependent sporulation, antioxidant defense, eisosome biogenesis, and the biosynthesis of trehalose and polyols-key metabolites supporting spore maturation and dormancy. Importantly, AtfA acts predominantly as a transcriptional activator, and its regulatory scope extends beyond stress adaptation to the orchestration of metabolic processes essential for spore integrity and germination. These findings position AtfA as a master integrator that synchronizes morphological development with metabolic preparedness during asexual reproduction in A. nidulans.