The yeast transcriptome in aerobic and hypoxic conditions: effects of hap1, rox1, rox3 and srb10 deletions

Abstract

SummaryThe transcriptome of Saccharomyces cerevisiae was screened using the high-density membrane hybridization method, under aerobic and hypoxic conditions, in wild-type and mutant backgrounds obtained by the disruption of the genes encoding the regulatory proteins Hap1, Rox1 and the Srb10 and Rox3 subunits of RNA polymerase II holoenzyme. None of the mutations studied was able to fully overcome the wild-type hypoxic response. Deletion of the hap1 gene changed the expression profiles of individual open reading frames (ORFs) under both aerobic and hypoxic conditions. Major changes associated with rox3 deletion were related to the hypoxic activation. Rox3 also caused a repressor effect (oxygen-independent) on a subset of genes related to subtelomeric proteins. With regard to the effect brought about by the deletion of rox1 and srb10, correspondence cluster analysis revealed that the transcriptome profile in aerobic conditions is very similar in the wild-type and both deletion strains. In contrast, however, differences were found during hypoxia between the subgroup formed by wild-type and the Drox1 deletant compared with the Dsrb10 deletant. An analysis of selected ORFs responding to hypoxia, in association with a dependence on the regulatory factors studied, made it possible to identify the clusters that are related to different regulatory circuits.

Investigating hypoxic tumor physiology through gene expression patterns

“…Under aerobic conditions, abundant heme activates the HAP1 complex that in turn transactivates the ROX1 gene. ROX1 protein blocks expression of a large set of hypoxia-responsive genes (Becerra et al, 2002). Under hypoxic conditions, heme-deficient HAP1 represses ROX1 transcription, and the hypoxia-responsive genes are derepressed (Zitomer et al, 1997).…”

Two-dimensional Transcriptome Analysis in Chemostat Cultures

“…This is exemplified by the enrichment of regulatory motifs in the consistently anaerobically induced transcripts (Table II). Clearly, regulation by known transcriptional regulators (relief of ROX1 repression and transcriptional activation by UPC2) (30,65,66) is not sufficient to account for the transcriptional response of all 65 genes that were consistently up-regulated under anaerobic conditions. Indeed, our study strongly suggests that at least a third factor, which recognizes an AAGGCAC motif, is involved in transcriptional regulation by oxygen availability.…”

Time-Course Analysis of Gene Expression During theSaccharomyces cerevisiaeHypoxic Response

“…One way that cells cope with changing oxygen levels is by dramatically altering gene expression (Semenza 2011; Butler 2013; Ratcliffe 2013). In the yeast Saccharomyces cerevisiae , several microarray studies have found that the mRNA levels of hundreds of genes change in response to hypoxia (ter Linde et al 1999; Becerra et al 2002; Ter Linde and Steensma 2002; Kwast et al 2002; Lai et al 2005, 2006; Hickman and Winston 2007; Hickman et al 2011). As might be expected, some responsive genes participate in oxygen-dependent cellular processes, such as aerobic respiration and the biosynthesis of unsaturated fatty acids (UFAs), heme, and ergosterol (the yeast functional equivalent of cholesterol).…”