Genome adaptation to chemical stress: clues from comparative transcriptomics in Saccharomyces cerevisiae and Candida glabrata

Comparative transcriptomics of Saccharomyces cerevisiae and Candida glabrata revealed a remarkable conservation of response to drug-induced stress, despite underlying differences in the regulatory networks

Structure and properties of transcriptional networks driving selenite stress response in yeasts

<p>Abstract</p> <p>Background</p> <p>Stress responses provide valuable models for deciphering the transcriptional networks controlling the adaptation of the cell to its environment. We analyzed the transcriptome response of yeast to toxic concentrations of selenite. We used gene network mapping tools to identify functional pathways and transcription factors involved in this response. We then used chromatin immunoprecipitation and knock-out experiments to investigate the role of some of these regulators and the regulatory connections between them.</p> <p>Results</p> <p>Selenite rapidly activates a battery of transcriptional circuits, including iron deprivation, oxidative stress and protein degradation responses. The mRNA levels of several transcriptional regulators are themselves regulated. We demonstrate the existence of a positive transcriptional loop connecting the regulator of proteasome expression, Rpn4p, to the pleiotropic drug response factor, Pdr1p. We also provide evidence for the involvement of this regulatory module in the oxidative stress response controlled by the Yap1p transcription factor and its conservation in the pathogenic yeast <it>C. glabrata</it>. In addition, we show that the drug resistance regulator gene <it>YRR1 </it>and the iron homeostasis regulator gene <it>AFT2 </it>are both directly regulated by Yap1p.</p> <p>Conclusion</p> <p>This work depicted a highly interconnected and complex transcriptional network involved in the adaptation of yeast genome expression to the presence of selenite in its chemical environment. It revealed the transcriptional regulation of <it>PDR1 </it>by Rpn4p, proposed a new role for the pleiotropic drug resistance network in stress response and demonstrated a direct regulatory connection between oxidative stress response and iron homeostasis.</p

Genome-Wide Transcriptome Analyses of Silicon Metabolism in Phaeodactylum tricornutum Reveal the Multilevel Regulation of Silicic Acid Transporters

BACKGROUND:Diatoms are largely responsible for production of biogenic silica in the global ocean. However, in surface seawater, Si(OH)(4) can be a major limiting factor for diatom productivity. Analyzing at the global scale the genes networks involved in Si transport and metabolism is critical in order to elucidate Si biomineralization, and to understand diatoms contribution to biogeochemical cycles. METHODOLOGY/PRINCIPAL FINDINGS:Using whole genome expression analyses we evaluated the transcriptional response to Si availability for the model species Phaeodactylum tricornutum. Among the differentially regulated genes we found genes involved in glutamine-nitrogen pathways, encoding putative extracellular matrix components, or involved in iron regulation. Some of these compounds may be good candidates for intracellular intermediates involved in silicic acid storage and/or intracellular transport, which are very important processes that remain mysterious in diatoms. Expression analyses and localization studies gave the first picture of the spatial distribution of a silicic acid transporter in a diatom model species, and support the existence of transcriptional and post-transcriptional regulations. CONCLUSIONS/SIGNIFICANCE:Our global analyses revealed that about one fourth of the differentially expressed genes are organized in clusters, underlying a possible evolution of P. tricornutum genome, and perhaps other pennate diatoms, toward a better optimization of its response to variable environmental stimuli. High fitness and adaptation of diatoms to various Si levels in marine environments might arise in part by global regulations from gene (expression level) to genomic (organization in clusters, dosage compensation by gene duplication), and by post-transcriptional regulation and spatial distribution of SIT proteins

Structure and properties of transcriptional networks driving selenite stress response in yeasts-3

Actors studied for selenite induction. DNA microarrays were used to compare gene expression levels between wild-type and , , or exposed to selenite (times 40, 60 and 80 minutes) or mock-treated (time 0). The 175 genes displaying an alteration of selenite induction in at least one mutant strain were clustered into 5 groups (see additional files and ). (B): Schematic representation of the importance of each transcription factor in the regulation of the five clusters defined in (A). The arrows symbolize the positive regulation of each cluster by the transcription factor: the width of the arrows indicates the importance of the regulation (large arrows: strong effect, thin arrows: weak effect). Dashed arrows indicate that the transcription factor controls the expression of only some of the genes present in the cluster. Solid arrows mean that all the genes present in the cluster are regulated. The relevance of the Gene Ontology categories and regulatory relationships in each of the clusters was investigated with the SGD GO term finder and Yeastract tools [,]. Only the main GO category with a p-value < 0.0001 and the main transcription factor known to regulate the genes in one cluster were indicated. (C): Enlargement of the part of cluster 1 containing the genes most sensitive to the deletion of and . Gene names are indicated. The presence of a PDRE in the promoters of these genes is indicated by black dots.<p><b>Copyright information:</b></p><p>Taken from "Structure and properties of transcriptional networks driving selenite stress response in yeasts"</p><p>http://www.biomedcentral.com/1471-2164/9/333</p><p>BMC Genomics 2008;9():333-333.</p><p>Published online 15 Jul 2008</p><p>PMCID:PMC2515152.</p><p></p

Structure and properties of transcriptional networks driving selenite stress response in yeasts-8

St to selenite. The color code is the same as for figure 1A. These predictions were based on previous ChIP-chip results []. (B): Expression patterns of genes encoding transcription factors involved in stress response pathways. Full results are presented in additional file . Wild-type cells were treated with selenite and gene expression was evaluated by microarray analyses at different time points, using untreated cells as a reference.<p><b>Copyright information:</b></p><p>Taken from "Structure and properties of transcriptional networks driving selenite stress response in yeasts"</p><p>http://www.biomedcentral.com/1471-2164/9/333</p><p>BMC Genomics 2008;9():333-333.</p><p>Published online 15 Jul 2008</p><p>PMCID:PMC2515152.</p><p></p

Structure and properties of transcriptional networks driving selenite stress response in yeasts-1

St to selenite. The color code is the same as for figure 1A. These predictions were based on previous ChIP-chip results []. (B): Expression patterns of genes encoding transcription factors involved in stress response pathways. Full results are presented in additional file . Wild-type cells were treated with selenite and gene expression was evaluated by microarray analyses at different time points, using untreated cells as a reference.<p><b>Copyright information:</b></p><p>Taken from "Structure and properties of transcriptional networks driving selenite stress response in yeasts"</p><p>http://www.biomedcentral.com/1471-2164/9/333</p><p>BMC Genomics 2008;9():333-333.</p><p>Published online 15 Jul 2008</p><p>PMCID:PMC2515152.</p><p></p

Structure and properties of transcriptional networks driving selenite stress response in yeasts-0

Tified through this study. All the arrows represent positive transcriptional regulations of transcription factor encoding genes or of groups of target genes (symbolized then by functional categories) by a transcription factor. Red arrows indicate interactions demonstrated for the first time by this work. The arrows in bold indicate high-weighted interactions and the thin arrows symbolize low-weighted interactions, according to the results of this study (in the case of Rpn4p, Yap1p, Pdr1p, Pdr3p) or measurements published by Hahn et al (in the case of Hsf1p) [].<p><b>Copyright information:</b></p><p>Taken from "Structure and properties of transcriptional networks driving selenite stress response in yeasts"</p><p>http://www.biomedcentral.com/1471-2164/9/333</p><p>BMC Genomics 2008;9():333-333.</p><p>Published online 15 Jul 2008</p><p>PMCID:PMC2515152.</p><p></p

Structure and properties of transcriptional networks driving selenite stress response in yeasts-4

Eal-time quantitative PCR, using strains harboring a chromosomal tagged version of Pdr1p (myc-Pdr1p). Sequence enrichment in the ChIP (i.e. ChIP/whole cell extract ratio) was normalized using the ORF as a reference. Similar experiments were conducted on cells with the untagged Pdr1p as a negative control ("mock ChIP"). The promoter was used as a positive control for Pdr1p binding. The results shown for were obtained using a pair of oligonucleotides spanning the PDRE motif present in the FLR1 promoter. The cells were exposed to 1 mM of selenite (+) or mock-treated (-) for 60 minutes before the beginning of the ChIP procedure.<p><b>Copyright information:</b></p><p>Taken from "Structure and properties of transcriptional networks driving selenite stress response in yeasts"</p><p>http://www.biomedcentral.com/1471-2164/9/333</p><p>BMC Genomics 2008;9():333-333.</p><p>Published online 15 Jul 2008</p><p>PMCID:PMC2515152.</p><p></p

Structure and properties of transcriptional networks driving selenite stress response in yeasts-5

Ent benomyl. The data obtained were analyzed and discussed fully in another manuscript (Lelandais et al., in preparation). (B) We searched for consensus DNA binding sites for Rpn4p, Yap1p and Pdr1p in the and promoters using RSA tools software []. The positions of the motifs identified are indicated relative to the start codon of the corresponding ORF. The species used here are , , , and . The positions of the motifs indicated for these species refer to the genes.<p><b>Copyright information:</b></p><p>Taken from "Structure and properties of transcriptional networks driving selenite stress response in yeasts"</p><p>http://www.biomedcentral.com/1471-2164/9/333</p><p>BMC Genomics 2008;9():333-333.</p><p>Published online 15 Jul 2008</p><p>PMCID:PMC2515152.</p><p></p