New Insights into the Pleiotropic Drug Resistance Network from Genome-Wide Characterization of the <i>YRR1</i> Transcription Factor Regulation System

Crom, Stéphane Le; Devaux, Frédéric; Marc, Philippe; Zhang, Xiaoting; Moye‐Rowley, W. Scott; Jacq, Claude

doi:10.1128/mcb.22.8.2642-2649.2002

Cited by 99 publications

(99 citation statements)

References 27 publications

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“…This is the case with CIN5, also named YAP4, whose function is not clear and which was already shown to be induced under conditions of either oxidative or osmotic stress (see reference 25 for a review). YRR1, which codes for a zinc finger transcription (7,19), is also activated by benomyl, probably via the activation of Yap1. The presence of Yap1 recognition elements in the promoters of both CIN5/YAP4 and YRR1 suggests a direct interaction of Yap1 with these promoters.…”

Section: Resultsmentioning

confidence: 99%

Early Expression of Yeast Genes Affected by Chemical Stress

Lucau-Danila

Lelandais

Kozovská

et al. 2005

Molecular and Cellular Biology

108

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The variety of environmental stresses is probably the major challenge imposed on transcription activators and the transcriptional machinery. To precisely describe the very early genomic response developed by yeast to accommodate a chemical stress, we performed time course analyses of the modifications of the yeast gene expression program which immediately follows the addition of the antimitotic drug benomyl. Similar analyses were conducted with different isogenic yeast strains in which genes coding for relevant transcription factors were deleted and coupled with efficient bioinformatics tools. Yap1 and Pdr1, two well-known key mediators of stress tolerance, appeared to be responsible for the very rapid establishment of a transient transcriptional response encompassing 119 genes. Yap1, which plays a predominant role in this response, binds, in vivo, promoters of genes which are not automatically up-regulated. We proposed that Yap1 nuclear localization and DNA binding are necessary but not sufficient to elicit the specificity of the chemical stress response.Cellular organisms develop a myriad of strategies to maintain specific internal conditions constantly challenged by the varying drug environment. The complexity of the yeast cell system for detecting and responding to environmental variations is only beginning to come to light. It has been reported previously (13) that a large set of yeast genes (about 900) showed a similar drastic response to a large variety of environmental changes including temperature shocks, hydrogen peroxide, menadione, diamide, dithiothreitol, hyper-or hypoosmotic shock, amino acid starvation, nitrogen source depletion, and progression into stationary phase. Since these pioneering studies were reported, many observations of the global effects of a large variety of drugs on gene expression have been made. In most of these studies, a binary comparison (i.e., control versus stress-exposed cells) was carried out, whereas in some cases, time course experiments over rather long periods (several hours) were conducted. Although much valuable information has been collected in these studies, the heterogeneity in the protocols followed precludes a simple comparison between the different drug responses. In particular, it is extremely difficult to identify the different regulatory networks and to establish their chronological relationships. Time series experiments soon appeared and were much more informative than simple binary experiments. Such approaches were a particularly valuable source of information in the case of cell cycle analyses (24, 27); however, they were less suitable to describe the chronology of transcriptional events in the case of environ-

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Section: Resultsmentioning

confidence: 99%

Early Expression of Yeast Genes Affected by Chemical Stress

Lucau-Danila

Lelandais

Kozovská

et al. 2005

Molecular and Cellular Biology

108

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“…In S. cerevisiae, pleiotropic drug resistance is not solely mediated by Pdr3 but may involve other regulators, viz. Pdr1, Pdr8, Yrr1 and its paralogue Yrm1 (DeRisi et al, 2000;Le Crom et al, 2002;Hikkel et al, 2003;Onda et al, 2004;Lucau-Danila et al, 2005). This response Transcriptional profiling of carotenoid-producing S. cerevisiae 991 C E N .…”

Section: Carotenoid Production Induces Expression Of Genes Involved Imentioning

confidence: 98%

“…We reasoned that carotenoids, which are hydrophobic compounds (Gruszecki and Strzalka, 2005), cannot readily dissolve in the media used for the growth of yeast strains but are more likely to remain attached to cellular membranes. To determine whether carotenoids could be secreted from Orange02 cells during growth in batch cultures, 20% v/v sunflower oil, which is a proper solvent * * * 0 (DeRisi et al, 2000;Le Crom et al, 2002;Devaux et al, 2002;Hikkel et al, 2003;Tuttle et al, 2003;Lucau-Danila et al, 2003;Onda et al, 2004 Nawrocki et al, 2001;Hikkel et al, 2003;Tuttle et al, 2003;Onda et al, 2004) PDR15 2 (Wolfger et al, 1997;DeRisi et al, 2000;Hikkel et al, 2003;Tuttle et al, 2003) YLR346C 3 (DeRisi et al, 2000;do Valle Matta et al, 2001;Le Crom et al, 2002;Devaux et al, 2002;Hikkel et al, 2003;Tuttle et al, 2003;Onda et al, 2004) PDR5 6 (DeRisi et al, 2000Miura et al, 2001;Devaux et al, 2002;Teixeira and Sa-Correia, 2002;Tuttle et al, 2003;Lucau-Danila et al, 2003;Onda et al, 2004;Wehrschutz-Sigl et al, 2004 DeRisi et al, 2000;Le Crom et al, 2002;Devaux et al, 2002;Hikkel et al, 2003;Tuttle et al, 2003;Lucau-Danila et al, 2003;Onda et al, 2...…”

Section: Carotenoid Secretion From Carotenoid-producing S Cerevisiaementioning

confidence: 99%

Heterologous carotenoid production in Saccharomyces cerevisiae induces the pleiotropic drug resistance stress response

Verwaal

Jiang

Wang

et al. 2010

Yeast

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To obtain insight into the genome-wide transcriptional response of heterologous carotenoid production in Saccharomyces cerevisiae, the transcriptome of two different S. cerevisiae strains overexpressing carotenogenic genes from the yeast Xanthophyllomyces dendrorhous grown in carbon-limited chemostat cultures was analysed. The strains exhibited different absolute carotenoid levels as well as different intermediate profiles. These discrepancies were further sustained by the difference of the transcriptional response exhibited by the two strains. Transcriptome analysis of the strain producing high carotenoid levels resulted in specific induction of genes involved in pleiotropic drug resistance (PDR). These genes encode ABC-type and major facilitator transporters which are reported to be involved in secretion of toxic compounds out of cells. β-Carotene was found to be secreted when sunflower oil was added to the medium of S. cerevisiae cells producing high levels of carotenoids, which was not observed when added to X. dendrorhous cells. Deletion of pdr10, one of the induced ABC transporters, decreased the transformation efficiency of a plasmid containing carotenogenic genes. The few transformants that were obtained had decreased growth rates and lower carotenoid production levels compared to a pdr5 deletion and a reference strain transformed with the same genes. Our results suggest that production of high amounts of carotenoids in S. cerevisiae leads to membrane stress, in which Pdr10 might play an important role, and a cellular response to secrete carotenoids out of the cell.

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“…These transcription factors have in common a Zn(2)-Cys(6) DNA-binding domain which targets sequences with direct, inverted, or everted palindromic repeats containing a 5Ј-CGG-3Ј motif with various numbers of nucleotides in the intervening spacer region. Several examples can be cited from studies performed with S. cerevisiae: Hap1p recognizes the direct repeat 5Ј-CGGNNNTANCGG-3Ј; the heterodimer Pip2p/Oaf1p binds to inverted repeats of the consensus sequence 5Ј-CGGN 15-18 -CCG-3Ј; Pdr8p and Yrr1p, which are factors involved in multidrug resistance, target DNA-binding motifs containing the 5Ј-CGG-3Ј triplet in dyad symmetry; and Pdr1p and Pdr3p regulate their targets via the everted sequence motif 5Ј-TCCG/aC/tGG/cA/g-3Ј (where lowercase letters indicate variable bases in a consensus motif) (9,17,23). More recently, it was shown that War1p binds the cis-acting element 5Ј-CGG-N 23 -CCG-3Ј, which is essential for PDR12 activation and resistance to weak acid stress (22).…”

Section: Discussionmentioning

confidence: 99%

TAC1 , Transcriptional Activator of CDR Genes, Is a New Transcription Factor Involved in the Regulation of Candida albicans ABC Transporters CDR1 and CDR2

Coste¹,

Karababa²,

Ischer³

et al. 2004

Eukaryot Cell

377

388

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The ABC transporter genes CDR1 and CDR2 can be upregulated in Candida albicans developing resistance to azoles or can be upregulated by exposing cells transiently to drugs such as fluphenazine. The cis-acting drug-responsive element (DRE) present in the promoters of both genes and necessary for their upregulation contains 5-CGG-3 triplets that are often recognized by transcriptional activators with Zn(2)-Cys(6) fingers. In order to isolate regulators of CDR1 and CDR2, the C. albicans genome was searched for genes encoding proteins with Zn(2)-Cys(6) fingers. Interestingly, three of these genes were tandemly arranged near the mating locus. Their involvement in CDR1 and CDR2 upregulation was addressed because a previous study demonstrated a link between mating locus homozygosity and azole resistance. The deletion of only one of these genes (orf19.3188) was sufficient to result in a loss of transient CDR1 and CDR2 upregulation by fluphenazine and was therefore named TAC1 (transcriptional activator of CDR genes). Tac1p has a nuclear localization, and a fusion of Tac1p with glutathione S-transferase could bind the cis-acting regulatory DRE in both the CDR1 and the CDR2 promoters. TAC1 is also relevant for azole resistance, since a TAC1 allele (TAC1-2) recovered from an azole-resistant strain could trigger constitutive upregulation of CDR1 and CDR2 in an azole-susceptible laboratory strain. Transcript profiling experiments performed with a TAC1 mutant and a revertant containing TAC1-2 revealed not only CDR1 and CDR2 as targets of TAC1 regulation but also other genes (RTA3, IFU5, and HSP12) that interestingly contained a DRE-like element in their promoters. In conclusion, TAC1 appears to be the first C. albicans transcription factor involved in the control of genes mediating antifungal resistance.

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New Insights into the Pleiotropic Drug Resistance Network from Genome-Wide Characterization of the YRR1 Transcription Factor Regulation System

Cited by 99 publications

References 27 publications

Early Expression of Yeast Genes Affected by Chemical Stress

Early Expression of Yeast Genes Affected by Chemical Stress

Heterologous carotenoid production in Saccharomyces cerevisiae induces the pleiotropic drug resistance stress response

TAC1 , Transcriptional Activator of CDR Genes, Is a New Transcription Factor Involved in the Regulation of Candida albicans ABC Transporters CDR1 and CDR2

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