General stress response or adaptation to rapid growth in Aspergillus nidulans?

Genome-wide transcriptional changes in Aspergillus nidulans induced by nine different stress conditions were evaluated to reveal the general environmental stress response gene set showing unidirectional expressional changes under various types of stress. Clustering the genes by their transcriptional changes was a useful technique for identifying large groups of co-regulated genes. Altogether, 1642 co-upregulated and 3916 co-downregulated genes were identified. Nevertheless, the co-regulated genes describe the difference between the transcriptomes recorded under the stress conditions tested and one chosen reference culture condition which is designated as the "unstressed" condition. Obviously, the corresponding transcriptional differences may be attributed to either the general stress response or the reference condition. Accordingly, reduced growth and increased transcription of certain antioxidative enzymes observed under stress may be interpreted as elements of the general stress response or as a feature of the "optimal growth" reference condition and decreased antioxidative protection due to "rapid growth" stress. Reversing the many to one comparison underlying the identification of co-regulated gene sets allows the same procedure to highlight changes under a single condition with respect to a set of other "background" conditions. As an example, we compared menadione treatment to our other conditions and identified downregulation of endoplasmic reticulum dependent processes and upregulation of iron-sulfur cluster assembly as well as glutathione-S-transferase genes as changes characteristic of MSB-treated cultures. Deletion of the atfA gene markedly altered the co-regulated gene sets primarily by changing the reference transcriptome; not by changing the stress responsiveness of genes. The functional characterization of AtfA-dependent co-regulated genes demonstrated the involvement of AtfA in the regulation of both vegetative growth and conidiogenesis in untreated cultures. Our data also suggested that the diverse effects of atfA gene deletion on the transcriptome under different stress conditions were the consequence of the altered transcription of several phosphorelay signal transduction system genes, including fphA, nikA, phkA, srrB, srrC, sskA and tcsB. Hopefully, this study will draw further attention to the importance of the proper selection of reference cultures in fungal transcriptomics studies especially when elements of specific stress responses are mapped.