Abstract:What steps are required for a promoter to acquire regulation by an environmental condition? We address this question by examining a promoter in Candida glabrata that is regulated by phosphate starvation and the transcription factor Pho4. The gene PMU2 encodes a secreted acid phosphatase that resulted from gene duplication events not present in other Ascomycetes, and only this gene of the three paralogs has acquired Pho4 regulation. We observe that the PMU2 promoter from C. glabrata is not functional in Sacchar… Show more
“…HOR2 in S. cerevisiae vs RHR2 in C. glabrata ) or evolutionarily unrelated (e.g. the phosphatase function of PHO5 in S. cerevisiae is replaced by that of PMU2 in C. glabrata ) (Figure 6A, Figure 6—source data 2, [Kerwin and Wykoff, 2009, 2012; Orlando et al, 2015]).10.7554/eLife.25157.016Figure 6.Functional annotation of Pho4 targets in C. glabrata .( A ) Comparison between all 24 ScPho4 targets in S. cerevisiae and CgPho4 targets with phosphate homeostasis related functions in C. glabrata . Abbreviations: ‘Poly P’ stands for ‘Polyphosphate’.…”
Section: Resultsmentioning
confidence: 99%
“…In terms of constraint, the core transcriptional regulator Pho4 is conserved as a single copy gene and regulates the phosphate starvation response in distantly related species such as S. cerevisiae and C. albicans (Ikeh et al, 2016). Second, the mechanism for regulating Pho4 activity in response to phosphate starvation is conserved between C. glabrata and S. cerevisiae – in both species, Pho4 nuclear localization is phosphorylation-dependent, controlled by homologous cyclin-dependent kinase complexes (Kerwin and Wykoff, 2012). Third, both CgPho4 and ScPho4 recognize the E-box motif ‘CACGTG’ (Materials and methods).…”
Although combinatorial regulation is a common feature in gene regulatory networks, how it evolves and affects network structure and function is not well understood. In S. cerevisiae, the phosphate starvation (PHO) responsive transcription factors Pho4 and Pho2 are required for gene induction and survival during phosphate starvation. In the related human commensal C. glabrata, Pho4 is required but Pho2 is dispensable for survival in phosphate starvation and is only partially required for inducing PHO genes. Phylogenetic survey suggests that reduced dependence on Pho2 evolved in C. glabrata and closely related species. In S. cerevisiae, less Pho2-dependent Pho4 orthologs induce more genes. In C. glabrata, its Pho4 binds to more locations and induces three times as many genes as Pho4 in S. cerevisiae does. Our work shows how evolution of combinatorial regulation allows for rapid expansion of a gene regulatory network’s targets, possibly extending its physiological functions.DOI:
http://dx.doi.org/10.7554/eLife.25157.001
“…HOR2 in S. cerevisiae vs RHR2 in C. glabrata ) or evolutionarily unrelated (e.g. the phosphatase function of PHO5 in S. cerevisiae is replaced by that of PMU2 in C. glabrata ) (Figure 6A, Figure 6—source data 2, [Kerwin and Wykoff, 2009, 2012; Orlando et al, 2015]).10.7554/eLife.25157.016Figure 6.Functional annotation of Pho4 targets in C. glabrata .( A ) Comparison between all 24 ScPho4 targets in S. cerevisiae and CgPho4 targets with phosphate homeostasis related functions in C. glabrata . Abbreviations: ‘Poly P’ stands for ‘Polyphosphate’.…”
Section: Resultsmentioning
confidence: 99%
“…In terms of constraint, the core transcriptional regulator Pho4 is conserved as a single copy gene and regulates the phosphate starvation response in distantly related species such as S. cerevisiae and C. albicans (Ikeh et al, 2016). Second, the mechanism for regulating Pho4 activity in response to phosphate starvation is conserved between C. glabrata and S. cerevisiae – in both species, Pho4 nuclear localization is phosphorylation-dependent, controlled by homologous cyclin-dependent kinase complexes (Kerwin and Wykoff, 2012). Third, both CgPho4 and ScPho4 recognize the E-box motif ‘CACGTG’ (Materials and methods).…”
Although combinatorial regulation is a common feature in gene regulatory networks, how it evolves and affects network structure and function is not well understood. In S. cerevisiae, the phosphate starvation (PHO) responsive transcription factors Pho4 and Pho2 are required for gene induction and survival during phosphate starvation. In the related human commensal C. glabrata, Pho4 is required but Pho2 is dispensable for survival in phosphate starvation and is only partially required for inducing PHO genes. Phylogenetic survey suggests that reduced dependence on Pho2 evolved in C. glabrata and closely related species. In S. cerevisiae, less Pho2-dependent Pho4 orthologs induce more genes. In C. glabrata, its Pho4 binds to more locations and induces three times as many genes as Pho4 in S. cerevisiae does. Our work shows how evolution of combinatorial regulation allows for rapid expansion of a gene regulatory network’s targets, possibly extending its physiological functions.DOI:
http://dx.doi.org/10.7554/eLife.25157.001
“…Researchers are lucky in that the relatedness of C. glabrata to S. cerevisiae also extends to the ease with which they can be grown in the laboratory, and with which they can be transformed and their genes manipulated. A series of molecular tools have been developed specifically for C. glabrata , the first plasmids dating from the 1990s (Mehra et al ., ; Zhou et al , ), and recently, inducible expression plasmids have been constructed (Kerwin and Wykoff, ; Zordan et al ., ). A ku – 1mutant has also been constructed in order to increase the efficiency of homologous targeting in the genome, by disadvantaging the non‐homologous end‐joining (NHEJ) pathway (Ueno et al ., ).…”
Section: History Of An Emerging Pathogenmentioning
The yeast Candida glabrata has become a major fungal opportunistic pathogen of humans since the 1980s. Contrary to what its name suggests, it is much closer, phylogenetically, to the model yeast Saccharomyces cerevisiae than to the most prevalent human fungal pathogen, Candida albicans. Its similarity to S. cerevisiae fortunately extends to their amenability to molecular genetics methods. C. glabrata is now described as part of the Nakaseomyces clade, which includes two new pathogens and other environmental species. C. glabrata is likely a commensal species of the human digestive tract, but systemic infections of immunocompromised patients are often fatal. In addition to being the subject of active medical research, other studies on C. glabrata focus on fundamental aspects of evolution of yeast genomes and adaptation. For example, the genome of C. glabrata has undergone major gene and intron loss compared to S. cerevisiae. It is also an apparently asexual species, a feature that inevitably leads to questions about the species' evolutionary past, present and future. On-going research with this yeast continues to address various aspects of adaptation to the human host and mechanisms of evolution in the Saccharomycetaceae, major model organisms for biology.
“…The key components of the PHO signalling pathway include the cyclin/cyclin‐dependent kinase complex Pho80p/Pho85p and Pho81p, which regulates the migration of the Pho4p transcription factor in response to Pi conditions (Kaffman et al ., ; Oneill et al ., ). Recently, it has been determined that phosphate starvation‐regulated promoters in Candida glabrata do not require Pho2p, a co‐activator that is required for the activation of phosphate‐responsive genes as well as Pho4p in S. cerevisiae (Kerwin and Wykoff, ).…”
SummaryIn Saccharomyces cerevisiae, PHM8 encodes a phosphatase that catalyses the dephosphorylation of lysophosphatidic acids to monoacylglycerol and nucleotide monophosphate to nucleoside and releases free phosphate. In this report, we investigated the role of PHM8 in triacylglycerol metabolism and its transcriptional regulation by a phosphate responsive transcription factor Pho4p under lowphosphate conditions. We found that the wild-type (BY4741) cells accumulate triacylglycerol and the expression of PHM8 was high under low-phosphate conditions. Overexpression of PHM8 in the wildtype, phm8Δ and quadruple phosphatase mutant (pah1Δdpp1Δlpp1Δapp1Δ) caused an increase in the triacylglycerol levels. However, the introduction of the PHM8 deletion into the quadruple phosphatase mutant resulted in a reduction in triacylglycerol levels and LPA phosphatase activity. The transcriptional activator Pho4p binds to the PHM8 promoter under low-phosphate conditions, activating PHM8 expression, which leads to the formation of monoacylglycerol from LPA. The synthesized monoacylglycerol is acylated to diacylglycerol by Dga1p, which is further acylated to triacylglycerol by the same enzyme.
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