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GSE13874
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Calcium signaling is a central regulator of cardiomyocyte growth and function. Calmodulin is a critical mediator of calcium signals. Because the amount of calmodulin within cardiomyocytes is limiting, precise regulation of calmodulin expression may be an important for regulation of calcium signaling. In this study, we show for the first time that calmodulin levels are regulated post-transcriptionally in heart failure. The cardiomyocyte-restricted microRNA miR-1 inhibited translation of calmodulin-encoding mRNAs via highly conserved target sites within their 3-untranslated regions. In keeping with its effect on calmodulin expression, miR-1 downregulated calcium-calmodulin signaling through the calcineurin to NFAT. miR-1 also negatively regulated expression of Mef2a and Gata4, key transcription factors that mediate calcium-dependent changes in gene expression. Consistent with downregulation of these hypertrophy-associated genes, miR-1 attenuated cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes and in the intact adult heart. Our data indicate that miR-1 regulates cardiomyocyte growth responses by negatively regulating the calcium-signaling components calmodulin, Mef2a, and Gata4.
Publication Title
MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
An important event in the pathogenesis of heart failure is the development of pathological cardiac hypertrophy. In cultured cardiac cardiomyocytes, the transcription factor Gata4 is required for agonist-induced cardiomyocyte hypertrophy. We hypothesized that in the intact organism Gata4 is an important regulator of postnatal heart function and of the hypertrophic response of the heart to pathological stress. To test this hypothesis, we studied mice heterozygous for deletion of the second exon of Gata4 (G4D). At baseline, G4D mice had mild systolic and diastolic dysfunction associated with reduced heart weight and decreased cardiomyocyte number. After transverse aortic constriction (TAC), G4D mice developed overt heart failure and eccentric cardiac hypertrophy, associated with significantly increased fibrosis and cardiomyocyte apoptosis. Inhibition of apoptosis by overexpression of the insulin-like growth factor 1 receptor prevented TAC-induced heart failure in G4D mice. Unlike WT-TAC controls, G4D-TAC cardiomyocytes hypertrophied by increasing in length more than width. Gene expression profiling revealed upregulation of genes associated with apoptosis and
Publication Title
Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
RPS19 mutations are the most common cause of the human disorder Diamond Blackfan Anemia. The R62W mutation was hypothesized to act in a dominant negative fashion and mice expressing RPS19R62W have many of the characteristics of Diamond Blackfan Anemia.
Publication Title
A transgenic mouse model demonstrates a dominant negative effect of a point mutation in the RPS19 gene associated with Diamond-Blackfan anemia.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The embryo lethal adenosine methylase tDNA knockout line SALK_074069 was partially complemented with its cDNA driven by the embryo specific ABI3 promoter (A6 lines). The plants have reduced adenosine methylation and show pleiotropic phenotypes. Rosette leaves were harvested from 3 week old plants, both wild-type and mutant plants in triplicate and analysed using the Affymetrix ATH1 array.
Publication Title
Adenosine Methylation in Arabidopsis mRNA is Associated with the 3' End and Reduced Levels Cause Developmental Defects.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Methylation of mRNA at the N6 position of adenosin is known for a long time, but its function remains poorly understood. Here generated a null mutant in the catalytic subunit of the m6A mRNA methylosome, dIME4, in Drosophila to determine the impact of loss of m6A on gene expression using Illumina sequencing. Overall design: Since dIME4 is preferentially expressed in the nervous system and dIME4 null mutants are viable, we compared gene expression and alternative splicing in wild type (2 samples) and dIME4 mutants (3 samples) with genetic background matched w control females in neuron enriched head/thorax.
Publication Title
m<sup>6</sup>A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 5 Downloadable Samples
- Illumina HiSeq 2500
Description
Methylation of mRNA at the N6 position of adenosin is known for a long time, but its function remains poorly understood. Here generated a null mutant in the catalytic subunit of the m6A mRNA methylosome, dIME4, in Drosophila to determine the impact of loss of m6A on gene expression using Illumina sequencing. Overall design: Since dIME4 is preferentially expressed in the nervous system and dIME4 null mutants are viable, we compared gene expression and alternative splicing in wild type (2 samples) and dIME4 mutants (3 samples) with genetic background matched w control females in neuron enriched head/thorax.
Publication Title
m<sup>6</sup>A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Aim of this project was the evaluation of the effect of flushing (intraportal and intraoperative) hepatic allografts with tacrolimus before transplantation. Group A was administered tacrolimus, 20ng/ml in 1500ml albumin solution; and Group B was administered only albumin solution. Wedge biopsie of the allograft were harvested after 15 min flushing time and the gene expression profile were determined.
Publication Title
Effect of intraportal infusion of tacrolimus on ischaemic reperfusion injury in orthotopic liver transplantation: a randomized controlled trial.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Staphylococcus aureus
- 17 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
More than 200 direct CodY target genes in Staphylococcus aureus were identified by genome-wide analysis of in vitro DNA binding. This analysis, which was confirmed for some genes by DNase I footprinting assays, revealed that CodY is a direct regulator of numerous transcription units associated with amino acid biosynthesis, transport of macromolecules and virulence. The virulence genes regulated by CodY fell into three groups. One group was dependent on the Agr system for its expression; these genes were indirectly regulated by CodY through its repression of the agr locus. A second group was regulated directly by CodY. The third group, which includes genes for alpha-toxin and capsule synthesis, was regulated by CodY in two ways, i.e., by direct repression and by repression of the agr locus. Since S. aureus CodY was activated in vitro by the branched chain amino acids and GTP, CodY appears to link changes in intracellular metabolite pools with the induction of numerous adaptive responses, including virulence.
Publication Title
Direct targets of CodY in Staphylococcus aureus.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
RRP1B is a breast cancer metastasis suppressor that interacts with various regulators of gene transcription
Publication Title
Metastasis-associated protein ribosomal RNA processing 1 homolog B (RRP1B) modulates metastasis through regulation of histone methylation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
EKLF is a Krppel-like transcription factor identified as a transcriptional activator and chromatin modifier in erythroid cells. EKLF-deficient (Eklf -/-) mice die at day 14.5 of gestation from severe anemia. In this study, we demonstrate that early progenitor cells fail to undergo terminal erythroid differention in Eklf -/- embryos. To discover potential EKLF target genes responsible for the failure of erythropoiesis, transcriptional profiling was performed with RNA from wild type and Eklf -/- early erythroid progenitor cells. These analyses identified significant perturbation of a network of genes involved in cell cycle regulation, with the critical regulator of the cell cycle, E2f2, at a hub. E2f2 mRNA and protein levels were markedly decreased in Eklf -/- early erythroid progenitor cells, which showed a delay in the G1-to-S-phase transition. Chromatin immunoprecipitation analysis demonstrated EKLF occupancy at the proximal E2f2 promoter in vivo. Consistent with the role of EKLF as a chromatin modifier, EKLF binding-sites in the E2f2 promoter were located in a region of EKLF-dependent DNase I sensitivity in early erythroid progenitor cells. We propose a model in which EKLF-dependent activation and modification of the E2f2 locus is required for cell cycle progression preceding terminal erythroid differentiation.
Publication Title
Failure of terminal erythroid differentiation in EKLF-deficient mice is associated with cell cycle perturbation and reduced expression of E2F2.
Sample Metadata Fields
Age, Specimen part
View Samples