Control of gene expression
Lai et al. (2005) examined the dynamic remodelling of the transcriptome during acclimatization to short-term anaerobiosis (two generations) under different metabolic states (catabolite-repressed or -derepressed). They determined that shifting cells from aerobic to anaerobic conditions in galactose medium induced an acute, yet transitory induction of Msn2p- and/or Msn4p-regulated genes associated with the retooling of reserve energy and catabolic pathways during the switch from respiro- fermentative to strictly fermentative growth. These changes are involved in balancing energetic supply and demand during this transition. Concomitantly, genes associated with the G1/S transition phase of the cell cycle were transiently down-regulated, resulting in a temporary arrest in the cell cycle. None ofthese networks were differentially expressed when cells experienced anaerobic shift in the presence of glucose, suggesting that a metabolically derived signal arising from the abrupt cessation of respiration, rather than O2 deprivation, elicits this ‘stress response' In both media, under anaerobic conditions, more chronic, haem-dependant effects were observed, including the down-regulation of Hap1p- and possibly Hap2/3/4/5p-regulated networks, derepression of Rox1p-regulated networks, and, following a slight delay, activation of Upc2p-regu- lated networks. These changes result in functional remodelling of sterol and sphingolipid metabolism, the cell wall, and dissimilatory pathways required for long-term anaerobiosis (Lai et al., 2005).
Ter Linde et al. (1999) and James et al. (2003) studied the transcription profiles of yeast during anaerobic incubation in chemostat culture and tall tube fermentations, respectively (ter Linde et al., 1999; James et al., 2003). During anaerobiosis, a number of genes, previously shown to respond to hypoxic conditions, were induced. These include ERG11, NCP1, AAC3, COX5, HEM13, OLE1, and the PAU gene family (Rachidi et al., 2000), which encodes the seripauperin proteins. Interestingly, 13 ORFs of unknown function, demonstrating homology to the PAU genes, are also induced under these fermentation conditions. Members of the anaerobiosis-inducible mannoprotein DAN/TIR family are also highly induced under these conditions. Additionally, transcript levels for the hypoxic gene AAC3, which is transcribed optimally under anoxic or microaerophilic conditions, were also up- regulated.
Under anaerobic conditions, cells cannot synthesize UFA or sterols (Lorenz and Parks, 1991). An exogenous source of UFA and sterol is essential for long-term anaerobic growth in S. cerevisiae (Andreasen and Stier, 1953, 1954). Lai et al. (2005) showed that transcriptomic remodelling during anaerobiosis is fairly specific for sterol and sphingolipid pathways, with very few genes specific for phospholipid or fatty acid synthesis (save for OLE1 and AAC1) showing changes in expression. Genes in the early portion of the sterol synthesis pathway exhibit complex expression patterns, with some showing transient (ERG10) or chronic up- regulation (IDI1 and HMG2) and others showing transient (ERG8 and MVD1) or chronic down- regulation (ERG13, ERG20 and HMG1). Nearly all the genes in the downstream steps of the pathway were chronically up-regulated, as were genes involved in transport (PDR11 and AUS1) and their primary regulator (UPC2).