Changes of global gene expression and secondary metabolite accumulation during light-dependent Aspergillus nidulans development.

Fungal development and secondary metabolite production are coordinated by regulatory complexes as the trimeric velvet complex. Light accelerates asexual but decreases sexual development of the filamentous fungus Aspergillus nidulans. Changes in gene expression and secondary metabolite accumulation in response to environmental stimuli have been the focus of many studies, but a comprehensive comparison during entire development is lacking. We compared snapshots of transcript and metabolite profiles during fungal development in dark or light. Overall 2.014 genes corresponding to 19% of the genome were differentially expressed when submerged vegetative hyphae were compared to surface development. Differentiation was preferentially asexual in light or preferentially sexual connected to delayed asexual development in dark. Light induces significantly gene expression within the first 24-48h after the transfer to surfaces. Many light induced genes are also expressed in dark after a delay of up to two days, which might be required for preparation of enhanced sexual development. Darkness results in a massive transcriptional reprogramming causing a peak of lipid-derived fungal pheromone synthesis (psi factors) during early sexual development and the expression of genes for cell-wall degradation presumably to mobilize the energy for sexual differentiation. Accumulation of secondary metabolites like antitumoral terrequinone A or like emericellamide start under light conditions, whereas the mycotoxin sterigmatocystin or asperthecin and emodin appear under dark conditions during sexual development. Amino acid synthesis and pool rapidly drop after 72-96h in dark. Subsequent initiation of apoptotic cell-death pathways in darkness happens significantly later than in light. This illustrates that fungal adaptation in differentiation and secondary metabolite production to light conditions requires the reprogramming of one fifth of the potential of its genome.

The COP9 signalosome mediates transcriptional and metabolic response to hormones, oxidative stress protection and cell wall rearrangement during fungal development.

The COP9 signalosome complex (CSN) is a crucial regulator of ubiquitin ligases. Defects in CSN result in embryonic impairment and death in higher eukaryotes, whereas the filamentous fungus Aspergillus nidulans survives without CSN, but is unable to complete sexual development. We investigated overall impact of CSN activity on A. nidulans cells by combined transcriptome, proteome and metabolome analysis. Absence of csn5/csnE affects transcription of at least 15% of genes during development, including numerous oxidoreductases. csnE deletion leads to changes in the fungal proteome indicating impaired redox regulation and hypersensitivity to oxidative stress. CSN promotes the formation of asexual spores by regulating developmental hormones produced by PpoA and PpoC dioxygenases. We identify more than 100 metabolites, including orsellinic acid derivatives, accumulating preferentially in the csnE mutant. We also show that CSN is required to activate glucanases and other cell wall recycling enzymes during development. These findings suggest a dual role for CSN during development: it is required early for protection against oxidative stress and hormone regulation and is later essential for control of the secondary metabolism and cell wall rearrangement.

Posttranscriptional regulation of FLO11 upon amino acid starvation in Saccharomyces cerevisiae.

Various starvation conditions cause adhesive growth of haploid cells or pseudohyphae formation of diploid cells of Saccharomyces cerevisiae. For the genetic Sigma1278b background, these morphological changes depend on the expression of the gene encoding the cell wall glycoprotein Flo11p, which is increased during nutritional limitations. Deletion of the genes encoding the transcriptional coactivators Rsc1p or Gcn5p impairs FLO11 transcription, which consequently leads to a loss of both haploid invasive growth and diploid pseudohyphae development upon glucose and nitrogen limitation, respectively. In contrast, amino acid starvation induces FLO11-dependent adhesive growth of the rsc1Delta and gcn5Delta strains although FLO11 transcription remains very low. The double deletion strain rsc1Deltaflo11Delta, however, does not grow adhesively, suggesting that the adhesion of the rsc1Delta strain at amino acid starvation is still FLO11-dependent. The FLO11prom-lacZ-encoded beta-galactosidase activities of the rsc1Delta and gcn5Delta mutant strains increase manifold upon amino acid starvation. It is therefore concluded that low levels of FLO11 transcripts are essential and sufficient for derepression of FLO11 expression and adhesive growth during amino acid starvation. A posttranscriptional control is assumed to be behind this phenomenon that permits the increased FLO11 expression from low FLO11 transcript abundances.