Rerep-Seq of copper resistant yeast
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA698368 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13593269_1.fastq.gz | Fastqsanger.gz | |||
| SRR13593269_2.fastq.gz | Fastqsanger.gz | |||
| SRR13593270_1.fastq.gz | Fastqsanger.gz | |||
| SRR13593270_2.fastq.gz | Fastqsanger.gz | |||
| SRR13593271_1.fastq.gz | Fastqsanger.gz |
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Project description:Copper homeostasis is an important determinant for virulence of many human pathogenic fungi such as the highly prevalent yeast Candida albicans. However, beyond the copper transporter Ctr1, little is known regarding other genes or biological process that are affected by copper. To gain insight into the cellular processes that are modulated by copper abundance in C. albicans, we monitored the global gene expression dynamic under both copper depletion and excess using RNA-seq.
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Project description:The haploid and the heterozygous essential S.cerevisiae deletion pools were grown in the presence of compounds that cause copper metabolism phenotypes in zebrafish. These experimental samples were hybridized against DMSO control samples. The resulting hybridization pattern informs about sensitive and resistant yeast deletion mutants. This data is used to draw conclusions about potential target pathways of these compounds in the cell.
2010-02-20 | E-TABM-922 | biostudies-arrayexpress
Project description:Lovastatin and other statins inhibit HMG-CoA reductase, which carries out an early step in the sterol biosynthesis pathway. Statins lower cholesterol and are widely prescribed to prevent heart disease, but like many drugs, they can interact with nutritionally acquired metabolites. To probe these interactions, we explored the effect of a diverse library of metabolites on statin effectiveness using a Saccharomyces cerevisiae model. In yeast, treatment with lovastatin results in reduced growth. We combined lovastatin with the library of metabolites and found that copper and zinc ions impaired the ability of the statin to inhibit yeast growth. Using an integrated genomic and metabolomic approach, we found that lovastatin plus metal synergistically upregulated some sterol biosynthesis genes. This altered pattern of gene expression resulted in greater flux through the sterol biosynthesis pathway and an increase in ergosterol levels. Each sterol intermediate level was correlated with expression of the upstream gene. Thus, the ergosterol biosynthetic response induced by statin is enhanced by copper and zinc. In cultured mammalian cells, these metals also rescued statin growth inhibition. Because copper and zinc impair the ability of statin to reduce sterol biosynthesis, dietary intake of these metals could have clinical relevance for statin treatment in humans.
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Project description:We sought to examine whether nucleosomes participate in cellular copper homeostasis by directly catalyzing the reduction of copper, thereby producing the biousable cuprous ion. To test this hypothesis, we disrupted a potential copper coordination site of the nucleosome by mutating the histone H3 His113 residue to an asparagine (H113N) in the budding yeast. We observed that copper homeostasis was indeed perturbed in the H113N mutant. However, given the known roles of nucleosomes in regulating gene expression, it was reasonable to expect that the perturbation of copper homeostasis was due simply to a conincidental disrutpion of the tanscriptional regulation of genes important for copper metabolism. We performed polyA+ RNA sequencing of WT and H3H113N yeast strains in various conditions to assess whether gene expression alterations could account for the copper-related phenotypes.
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Project description:The effect of the heavy metal copper on the expression of a wide spectrum of genes was analyzed by using a DNA microarray. Gene expression profile of baker’s yeast Saccharomyces cerevisiae grown in a media containing sub-lethal concentration of cupric sulfate was compared with those of yeast grown in a normal media. Among about 6200 ORFs of yeast, 143 ORFs were induced more than two-fold to resist against copper toxicity after exposure to copper. As was expected, FRE1, FRE7, and CTR1, genes controlled by Mac1p, were strongly down-regulated. Copper metallothionein CUP1-1 and CUP1-2 were induced more than 20-fold. Some genes related to sulfur metabolism and oxidative stress response were also up-regulated. This DNA microarray technology indicated that plasma membrane, cell wall, protein, and DNA, were molecular targets of copper toxicity. Keywords: stress response
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Project description:Saccharomyces cerevisiae is exposed to freeze-thaw stress in commercial processes including frozen dough baking. The cell viability and fermentation activity after freeze-thaw were dramatically decreased due to freeze-thaw injury. Because freeze-thaw injury involves complex phenomena, the mechanisms of it are not fully understood. We attempted to analyze the mechanisms of freeze-thaw injury by indirect gene expression analysis during post-thaw incubation after freeze-thaw treatment using DNA microarray profiling. The results showed that a high frequency of the genes involved in the homeostasis of metal ions were up-regulated depending on the freezing period. The phenotype of the deletion mutants of the up-regulated genes extracted by indirect gene expression analysis was assessed. The deletion strains of the MAC1 and CTR1 genes involved in copper ion homeostasis exhibited freeze-thaw sensitivity, suggesting that copper ion homeostasis is required for freeze-thaw tolerance. Supplementation with copper ions during post-thaw incubation increased intracellular superoxide dismutase activity. Inverse correlated with intracellular superoxide dismutase activity, intracellular levels of reactive oxygen species were decreased. Moreover, cell viability increased by supplementation with copper ions under specific assessment conditions. This study suggested that insufficiency of copper ion homeostasis may be one of the causes of freeze-thaw injury. Total RNA was extracted from the stress-treated yeast cells by using a hot phenol method. Poly(A)+ RNA was enriched from total RNA by using an Oligotex dT30 (Super) mRNA purification kit (Takara Bio, Ohtsu, Japan). cDNA synthesis, cRNA synthesis, and labeling were performed according to the Affymetrix user’s manual (Affymetrix, Santa Clara, USA). Biotinyated cRNA was fragmented and then used as a probe.Affimetrix Yeast Genome 2.0 arrays (Affymetrix) were used as DNA microarrays. All experiments were done in triplicate independently.
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Project description:Chemotherapy resistance presents a major hurdle for cancer treatment. We proposed to identify the molecular changes through which breast cancer cells evolve resistance to conventional treatment, here cisplatin, so targeted therapy can be developed. Candidate approach RNAi screening was combined with cisplatin treatment in order to identify molecular pathways conferring survival advantages. The screening identified ATP7A, a copper transport ATPase responsible for the intercellular movement and sequestering of cisplatin, as a therapeutic target. Copper chelation with tetrathiomolybdate (TM) targets ATP7A. TM in combination with cisplatin sensitized drug-resistant breast cancer cells. Allograft and xenograft models in aythymic mice treated with TM/cisplatin combination therapy inhibited tumor growth and increased survival compared with monotreated mice. Examination of the molecular effects of TM on cisplatin efficacy in drug-resistant tumors revealed reduced levels of APT7A, reduced cisplatin sequestering by ATP7A and increased nuclear availability of cisplatin. Further, we showed that TM treatment combined with cisplatin reduced the half-life of ATP7A in human breast cancer cell lines. This finding offered the potential to combat drug platinum-resistant tumors and sensitize patients to conventional breast cancer treatments by identifying and targeting resistant tumors’ unique molecular adaptations.
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Project description:In our previous work, we showed the positive effect of the magnesium and the negative effect of the copper on yeast fermentation performance. The magnesium increases the ethanol yield and a faster glucose consumption by the yeast, on the other hand, the copper provides an opposite effect in yeast under fermentation condition. Therefore, from this contrasting effect we performed the gene-wide expression analysis in the industrial yeast Saccharomyces cerevisiae JP1 under fermentation condition in order to reveal the gene expression profile upon magnesium and copper supplementation.
2015-12-09 | GSE75803 | GEO
Project description:Copper and iron are essential micronutrients for most living organisms because they participate as cofactors in biological processes including respiration, photosynthesis and oxidative stress protection. In many eukaryotic organisms, including yeast and mammals, copper and iron homeostases are highly interconnected; however such interdependence is not well established in higher plants. Here we propose that COPT2, a high-affinity copper transport protein, functions under copper and iron deficiencies in Arabidopsis thaliana. COPT2 is a plasma membrane protein that functions in copper acquisition and distribution. Characterization of the COPT2 expression pattern indicates a synergic response to copper and iron limitation in roots. We have characterized a knockout of COPT2, copt2-1, that leads to increased resistance to simultaneous copper and iron deficiencies, measured as reduced leaf chlorosis and improved maintenance of the photosynthetic apparatus. We propose that COPT2 expression could play a dual role under Fe deficiency. First, COPT2 participates in the attenuation of copper deficiency responses driven by iron limitation maybe aimed to minimize further iron consume. On the other hand, global expression analyses of copt2-1 mutants versus wild type Arabidopsis plants indicate that low phosphate responses are increased in copt2-1 plants. In this sense, COPT2 function under Fe deficiency counteracts low phosphate responses. These results open up new biotechnological approaches to fight iron deficiency in crops.
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Project description:NOT PROVIDED; REQUESTED
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