The Cyclin in the RNA Polymerase Holoenzyme Is a Target for the Transcriptional Repressor Tup1p in &lt;i&gt;Saccharomyces cerevisiae&lt;/i&gt;

Schüller, Jutta; Lehming, Norbert

doi:10.1159/000071071

Cited by 11 publications

(5 citation statements)

References 39 publications

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“…Interestingly, a kinase-deficient Asp290Ala Ssn3 only weakly phosphorylates Ste12 in vitro , and the lack of phosphorylation increases its stability [51] . Moreover, the catalytic activity of Ssn3 contributes to the repression of a subset of Tup1-regulated genes [81] – [83] in S. cerevisiae . Tup1 is recruited to promoters by Nrg1 [84] , a factor which was downregulated in the Evo strain.…”

Section: Discussionmentioning

confidence: 99%

Microevolution of Candida albicans in Macrophages Restores Filamentation in a Nonfilamentous Mutant

et al. 2014

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Following antifungal treatment, Candida albicans, and other human pathogenic fungi can undergo microevolution, which leads to the emergence of drug resistance. However, the capacity for microevolutionary adaptation of fungi goes beyond the development of resistance against antifungals. Here we used an experimental microevolution approach to show that one of the central pathogenicity mechanisms of C. albicans, the yeast-to-hyphae transition, can be subject to experimental evolution. The C. albicans cph1Δ/efg1Δ mutant is nonfilamentous, as central signaling pathways linking environmental cues to hyphal formation are disrupted. We subjected this mutant to constant selection pressure in the hostile environment of the macrophage phagosome. In a comparatively short time-frame, the mutant evolved the ability to escape macrophages by filamentation. In addition, the evolved mutant exhibited hyper-virulence in a murine infection model and an altered cell wall composition compared to the cph1Δ/efg1Δ strain. Moreover, the transcriptional regulation of hyphae-associated, and other pathogenicity-related genes became re-responsive to environmental cues in the evolved strain. We went on to identify the causative missense mutation via whole genome- and transcriptome-sequencing: a single nucleotide exchange took place within SSN3 that encodes a component of the Cdk8 module of the Mediator complex, which links transcription factors with the general transcription machinery. This mutation was responsible for the reconnection of the hyphal growth program with environmental signals in the evolved strain and was sufficient to bypass Efg1/Cph1-dependent filamentation. These data demonstrate that even central transcriptional networks can be remodeled very quickly under appropriate selection pressure.

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Section: Discussionmentioning

confidence: 99%

Microevolution of Candida albicans in Macrophages Restores Filamentation in a Nonfilamentous Mutant

et al. 2014

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“…In S. cerevisiae , interaction of Sc Srb10p with its kinase Sc Srb11p and with the general repressor of transcription Sc Tup1p has been demonstrated, and both interactions are related to the function of Sc Srb10p on transcriptional regulation (Kuchin and Carlson, 1998; Zaman et al , 2001; Schüller and Lehming, 2003). The complex Tup1–Ssn6 is a general co‐repressor in yeast but it does not bind directly to DNA (Keleher et al , 1992; Tzamarias and Struhl, 1994; Carrico and Zitomer, 1998).…”

Section: Resultsmentioning

confidence: 99%

“…In S. cerevisiae the function of Srb10p on transcriptional regulation implies multiple interactions with other proteins, among them the partner cyclin Srb11p and, for repression, with proteins from the co‐repressor Ssn6p–Tup1p complex (Kuchin and Carlson, 1998; Zaman et al , 2001; Schüller and Lehming, 2003). Using the two‐hybrid approach, we have found positive interaction between Kl Srb10p and Kl Srb11p (Table 3).…”

Section: Discussionmentioning

confidence: 99%

A functional analysis of KlSRB10: implications in Kluyveromyces lactis transcriptional regulation

Núñez

González-Siso

Rodrı́guez-Belmonte

et al. 2007

Yeast

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The function of KlSRB10 has been studied by diverse approaches. Primer extension analysis reveals several transcription start sites, position −17 from ATG being predominant. Deletion of KlSRB10 diminishes growth in ethanol and decreases KlCYC1 transcript levels. A second phenotype associated with this deletion affects growth in galactose. These phenotypes are independent of the specific sequence connecting the ATP binding cassette and the kinase domain of Srb10p in yeasts. Kl Srb10p is not necessary for LAC4 repression mediated by Kl Gal80p, as deduced by construction of a Klgal80 srb10 double mutant. In the two-hybrid system, Kl Srbp10p interacts with the protein encoded by KLLA0E08151g (Kl Srbp11p).

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“…The repressive role of the Mediator requires function of the Srb8 -11 module that is believed to inhibit association of RNA polymerase II with the Mediator and formation of the preinitiation complex (53,54). The co-repressor complex Tup1p/Ssn6p recruits Mediator to repressed promoters by physically interacting with Mediator components Med3p (55), Srb7p (56), Srb10p (57), and Srb11p (58). However, Tup1p/Ssn6p is probably not involved in recruitment of the Mediator to the FLR1 promotor, because FLR1 expression and benomyl resistance in the tup1⌬ mutant are increased much less than in med1⌬, med2⌬, and sin4⌬ mutants (Figs.…”

Section: Discussionmentioning

confidence: 99%

Expression of FLR1 Transporter Requires Phospholipase C and Is Repressed by Mediator

Romero¹,

Desai

DeLillo

et al. 2006

Journal of Biological Chemistry

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In budding yeast, phosphoinositide-specific phospholipase C (Plc1p encoded by PLC1 gene) is important for function of kinetochores. Deletion of PLC1 results in benomyl sensitivity, alterations in chromatin structure of centromeres, mitotic delay, and a higher frequency of chromosome loss. Here we intended to utilize benomyl sensitivity as a phenotype that would allow us to identify genes that are important for kinetochore function and are downstream of Plc1p. However, our screen identified SIN4, encoding a component of the Mediator complex of RNA polymerase II. Deletion of SIN4 gene (sin4⌬) does not suppress benomyl sensitivity of plc1⌬ cells by improving the function of kinetochores. Instead, benomyl sensitivity of plc1⌬ cells is caused by a defect in expression of FLR1, and the suppression of benomyl sensitivity in plc1⌬ sin4⌬ cells occurs by derepression of FLR1 transcription. FLR1 encodes a plasma membrane transporter that mediates resistance to benomyl. Several other mutations in the Mediator complex also result in significant derepression of FLR1 and greatly increased resistance to benomyl. Thus, benomyl sensitivity is not a phenotype exclusively associated with mitotic spindle defect. These results demonstrate that in addition to promoter-specific transcription factors that are components of the pleiotropic drug resistance network, expression of the membrane transporters can be regulated by Plc1p, a component of a signal transduction pathway, and by Mediator, a general transcription factor. The results thus suggest another layer of complexity in regulation of pleiotropic drug resistance.The hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C (PLC) 3 yields two prominent eukaryotic second messengers, 1,2-diacylglycerol and inositol 1,4,5-trisphosphate (IP 3 ). In higher eukaryotes, the hydrophilic IP 3 triggers the release of calcium from internal stores and thus modulates Ca 2ϩ /calmodulin-regulated pathways, whereas the hydrophobic 1,2-diacylglycerol activates the phospholipid-and Ca 2ϩ -dependent protein kinase C (1-3).In yeast cells, PLC (Plc1p encoded by PLC1) and three inositol polyphosphate (InsPs) kinases (Ipk2p/Arg82p, Ipk1p, and Kcs1p) constitute a nuclear signaling pathway that affects transcriptional control (4) and export of mRNA from the nucleus (5). Recently, InsPs produced by a Plc1p-dependent pathway have been shown to regulate the activity of chromatin remodeling complexes in vivo and in vitro (6, 7). The induction of the phosphate-responsive PHO5 gene, chromatin remodeling of its promoter, and recruitment of Swi/Snf and Ino80 chromatin remodeling complexes are impaired in the ipk2/arg82 mutant strain (7). In vitro, nucleosome mobilization by the yeast Swi/Snf complex is stimulated by IP 4 and IP 5 , whereas IP 6 inhibits nucleosome mobilization by yeast Isw2 and Ino80 complexes and Drosophila NURF complex (6). A possible mechanism by which InsPs affect chromatin remodeling may involve effects on protein conformation of the chromatin remodeling complexes (7). Alternativ...

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The Cyclin in the RNA Polymerase Holoenzyme Is a Target for the Transcriptional Repressor Tup1p in <i>Saccharomyces cerevisiae</i>

Cited by 11 publications

References 39 publications

Microevolution of Candida albicans in Macrophages Restores Filamentation in a Nonfilamentous Mutant

Microevolution of Candida albicans in Macrophages Restores Filamentation in a Nonfilamentous Mutant

A functional analysis of KlSRB10: implications in Kluyveromyces lactis transcriptional regulation

Expression of FLR1 Transporter Requires Phospholipase C and Is Repressed by Mediator

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