Global gene expression analysis of Aspergillus nidulans reveals metabolic shift and transcription suppression under hypoxia

Abstract

Hypoxia imposes a challenge upon most filamentous fungi that require oxygen for proliferation. Here, we used whole genome DNA microarrays to investigate global transcriptional changes in Aspergillus nidulans gene expression after exposure to hypoxia followed by normoxia. Aeration affected the expression of 2,864 genes (27% of the total number of genes in the fungus), of which 50% were either induced or repressed under hypoxic conditions. Up-regulated genes included those for glycolysis, ethanol production, the tricarboxylic acid (TCA) cycle, and for the γ-aminobutyrate (GABA) shunt that bypasses two steps of the TCA cycle. Ethanol and lactate production under hypoxic conditions indicated that glucose was fermented to these compounds via the glycolytic pathway. Since the GABA shunt bypasses the NADH-generating reaction of the TCA cycle catalyzed by oxoglutarate dehydrogenase, hypoxic A. nidulans cells eliminated excess NADH. Hypoxia down-regulated some genes involved in transcription initiation by RNA polymerase II, and lowered the cellular mRNA content. These functions were resumed by re-oxygenation, indicating that A. nidulans controls global transcription to adapt to a hypoxic environment. This study is the first to show that hypoxia elicits systematic transcriptional responses in A. nidulans.

Identification of Hypoxia-Inducible Target Genes of Aspergillus fumigatus by Transcriptome Analysis Reveals Cellular Respiration as an Important Contributor to Hypoxic Survival

“…Many similarities in the adaptation to hypoxia can be found when comparing our results with those from previous studies of Aspergillus species. As observed for A. nidulans and A. oryzae (18,20), intracellular trafficking processes and cytoskeletal transcripts were downregulated under hypoxic conditions, most probably in order to reduce ATP consumption. In contrast, genes participating in the glyoxylate pathway were upregulated under hypoxic conditions, whereas the regulation of glycolytic genes was heterogenous (see Data Set S1 in the supplemental material).…”

“…However, for A. fumigatus no growth phenotype was observed under oxygen-limiting conditions for strains devoid of ethanol fermentation (19). The ␥-aminobutyric acid (GABA) shunt pathway has also been proposed to bypass the accumulation of NADH in A. fumigatus and A. nidulans during hypoxic growth (12,20,21). Furthermore, in A. nidulans and Fusarium oxysporum, growth under oxygen-limiting conditions is supported by using nitrate as an alternative electron acceptor, a process also referred to as ammonia fermentation (22,23).…”

Expressions of oxidative stress-related genes and antioxidant enzyme activities in Mytilus galloprovincialis (Bivalvia, Mollusca) exposed to hypoxia

“…It was reported that high levels of ROS and high metabolic activity are involved in inducing the expression of the NADH dehydrogenase 1α subcomplex gene (Masuo et al 2010;Bruckbauer and Zemel 2011). We found that a low oxygen concentration reduced nad2 transcription in mussels, and the expression of the gene was downregulated by approximately an order of magnitude relative to the control group.…”

Sirtuin A regulates secondary metabolite production by <i>Aspergillus nidulans</i>

“…ing custom DNA microarrays created on GeneChip (Masuo et al, 2010). No difference was observed between the growth rates of SirAD and A26 strains.…”

“…Transcriptomes were analyzed using a custom-synthesized A. nidulans GeneChip (Masuo et al, 2010). The signal log 2 ratio between signals obtained for the A26 and SirAD cultures at each time point was normalized, processed as described (Masuo et al, 2010), and published in the data repository Gene Expression Omnibus (GEO) under accession number GSE85319. Genes that were ≥2-fold up-or down-regulated at one or more time points were grouped into three sets using k-means clustering analyses (Soukas et al, 2000).…”