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SRP050591
Saccharomyces cerevisiae
4 Downloadable Samples
Illumina HiSeq 2500
Description
As a result of ancestral whole genome and small-scale duplication events, the genome of Saccharomyces cerevisiae's, and of many eukaryotes, still contain a substantial fraction of duplicated genes. In all investigated organisms, metabolic pathways, and more particularly glycolysis, are specifically enriched for functionally redundant paralogs. In ancestors of the Saccharomyces lineage, the duplication of glycolytic genes is purported to have played an important role leading to S. cerevisiae current lifestyle favoring fermentative metabolism even in the presence of oxygen and characterized by a high glycolytic capacity. In modern S. cerevisiae, the 12 glycolytic reactions leading to the biochemical conversion from glucose to ethanol are encoded by 27 paralogs. In order to experimentally explore the physiological role of this genetic redundancy, a yeast strain with a minimal set of 14 paralogs was constructed (MG strain). Remarkably, a combination of quantitative, systems approach and of semi-quantitative analysis in a wide array of growth environments revealed the absence of phenotypic response to the cumulative deletion of 13 glycolytic paralogs. This observation indicates that duplication of glycolytic genes is not a prerequisite for achieving the high glycolytic fluxes and fermentative capacities that are characteristic for S. cerevisiae and essential for many of its industrial applications and argues against gene dosage effects as a means for fixing minor glycolytic paralogs in the yeast genome. MG was carefully designed and constructed to provide a robust, prototrophic platform for quantitative studies, and is made available to the scientific community. Overall design: The goals of the present study are to experimentally explore genetic redundancy in yeast glycolysis by cumulative deletion of minor paralogs and to provide a new experimental platform for fundamental yeast research by constructing a yeast strain with a functional 'minimal glycolysis'. To this end, we deleted 13 minor paralogs, leaving only the 14 major paralogs for the S. cerevisiae glycolytic pathway. The cumulative impact of deleting all minor paralogs was investigated by two complementary approaches. A first, quantitative analysis focused on the impact on glycolytic flux under a number of controlled cultivation conditions that, in wild-type strains, result in different glycolytic fluxes. These quantitative growth studies were combined with transcriptome, enzyme-activity and intracellular metabolite assays to capture potential small phenotypic effects. A second, semi-quantitative characterization explored the phenotype of the 'minimal glycolysis' strain under a wide array of experimental conditions to identify potential context-dependent phenotypes
Publication Title
The Genetic Makeup and Expression of the Glycolytic and Fermentative Pathways Are Highly Conserved Within the <i>Saccharomyces</i> Genus.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 200 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motives we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified co-regulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B cell and T cell infiltration. We calculated metagenes as surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with principal component analysis. Distinct patterns led to the hypothesis of a prognostic role of the immune system in tumors with high expression of proliferation associated genes. In multivariate Cox regression analysis the proliferation metagene showed a significant association with metastasis-free survival of the whole discovery cohort (Hazard Ratio (HR) 2.20, 95% confidence interval (CI) 1.40-3.46). The B cell metagene showed additional independent prognostic information in carcinomas with high proliferative activity (HR 0.66, 95% CI 0.46 - 0.97). A prognostic influence of the B-cell metagene was independently confirmed by multivariate analysis in a first validation cohort enriched for high grade tumors (n=286, HR 0.78, 95% CI 0.62-0.98), and a second validation cohort enriched for younger patients (n=302, HR 0.83, 95% CI 0.7-0.97). Thus, we could demonstrate in three cohorts of untreated node-negative breast cancer patients, that the humoral immune system plays a pivotal role for metastasis-free survival of carcinomas of the breast.
Publication Title
The humoral immune system has a key prognostic impact in node-negative breast cancer.
Sample Metadata Fields
Disease stage
View Samples- Arabidopsis thaliana
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
Seed development is sensitive to parental dosage, with excess maternal or paternal genomes creating reciprocal phenotypes. Paternal genomic excess results in extensive endosperm proliferation without cellularization and eventual seed abortion. We previously showed that loss of the RNA POL IV gene nrpd1 in tetraploid fathers represses seed abortion in paternal excess crosses. Here we show genetically that RNA-directed DNA methylation (RdDM) pathway activity in the paternal parent is sufficient to determine the viability of paternal excess seeds. The status of the RdDM pathway in paternal excess endosperm does not impact seed viability. Comparison of endosperm transcriptomes, DNA methylation, and small RNAs from balanced and paternal excess endosperm demonstrates that paternal excess seed abortion is unlikely to be dependent on either transposable element or imprinted gene mis-regulation. We suggest instead that loss of paternal RdDM modulates expression at a small subset of genes and desensitizes endosperm to paternal excess. Finally, using allele-specific transcription data, we present evidence of a transcriptional buffering system that up37 regulates maternal alleles and represses paternal alleles in response to excess paternal genomic dosage. These findings prompt reconsideration of models for dosage sensitivity in endosperm. Overall design: Examination of parent-of-origin specific and total gene expression in wild type and nrpd1 endosperm 6 days after pollination - 10 samples. Balanced (Replicate1) GSM2858422 Balanced (Replicate2) GSM2858423 Balanced (Replicate3) GSM2858424 Balanced (Replicate4) GSM2482916 Balanced (Replicate5) GSM2482917
Publication Title
Paternally Acting Canonical RNA-Directed DNA Methylation Pathway Genes Sensitize Arabidopsis Endosperm to Paternal Genome Dosage.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Nonsense-mediated mRNA decay (NMD) is a molecular pathway of mRNA surveillance that ensures rapid degradation of mRNAs containing premature translation termination codons (PTCs) in eukaryotes. Originally, NMD was thought of as a quality control pathway that targets non-functional mRNAs arising from mutations and splicing errors. More recently, NMD has been shown to also regulate normal gene expression and NMD thus emerged as one of the key post-transcriptional mechanisms of gene regulation. We have now systematically analyzed the molecular mechanism of variable NMD efficiency and used different HeLa cell strains as a model system. The results of this analysis show that NMD efficiency can be remarkably variable and represents a stable characteristic of these strains. Low NMD efficiency is shown to be functionally related to the reduced abundance of the exon junction component RNPS1 in one of the HeLa strain analyzed. Furthermore, restoration of functional RNPS1 expression, but not of NMD-inactive mutant proteins, also restores efficient NMD in the RNPS1 deficient cell line. We conclude that cellular concentrations of RNPS1 modify NMD efficiency and propose that the cell type specific co-factor availability represents a novel principle that controls NMD.
Publication Title
The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway.
Sample Metadata Fields
Sex, Disease, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To characterize gene response in RPE65-/- mouse model of Lebers congenital amaurosis during progression of the disease, we analyzed differential gene expression in retinae early in the development of the disease, namely before and at the onset of photoreceptor cell death in knock-out mice of 2, 4 and 6 months of age.
Publication Title
Biological characterization of gene response in Rpe65-/- mouse model of Leber's congenital amaurosis during progression of the disease.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Drosophila tdf, another name apontic (apt), encodes a bZIP transcription factor that is required for the development of trachea, heart, head and neural system. However, little is known about the target of TDF/Apt.
Publication Title
Evolutionarily conserved transcription factor Apontic controls the G1/S progression by inducing cyclin E during eye development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 225 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
These data, combined with other cohorts (GSE6532, GSE12093, and qRT-PCR based cohorts), was used to construct the EP algorithm, which predicts the likelihood of developing of a distant recurrence of early stage breast cancer under endocrine treatment. In addition, EPclin, a combination of the EP score, the nodal status and the tumor size, was constructed.
Publication Title
A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 40 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Critical role for TRIM28 and HP1β/γ in the epigenetic control of T cell metabolic reprograming and effector differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Critical role for TRIM28 and HP1b/g in the epigenetic control of T cell metabolic reprogramming and effector differentiation
Publication Title
Critical role for TRIM28 and HP1β/γ in the epigenetic control of T cell metabolic reprograming and effector differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Critical role for TRIM28 and HP1b/g in the epigenetic control of T cell metabolic reprogramming and effector differentiation
Publication Title
Critical role for TRIM28 and HP1β/γ in the epigenetic control of T cell metabolic reprograming and effector differentiation.
Sample Metadata Fields
Specimen part
View Samples