This SuperSeries is composed of the SubSeries listed below.
Interactions of chromatin context, binding site sequence content, and sequence evolution in stress-induced p53 occupancy and transactivation.
Cell line, Time
View SamplesTo determine if induced p53 binding is associated with gene expression in genome-wide. We examined mRNA levels with the Affymetrix Human Exon 1.0 ST platform in human lymphoblastoid GM12878 cells treated with doxorubicin to activate p53.
Interactions of chromatin context, binding site sequence content, and sequence evolution in stress-induced p53 occupancy and transactivation.
Cell line, Time
View SamplesTo determine if induced NRF2 binding is associated with gene expression in genome-wide. We examined mRNA levels with theAffymetrix Human Exon 1.0 ST platform in human lymphoblastoid GM12878 cells treated with sulforaphane to activate NRF2.
Beyond antioxidant genes in the ancient Nrf2 regulatory network.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptomic data from the rat liver after five days of exposure to legacy or emerging brominated flame retardants.
Sex, Specimen part, Treatment
View SamplesThe use of calcineurin inhibitor (CI) immunosuppressants has significantly improved the early allograft survival rate in organ transplantation. However, CI therapy has been associated with chronic nephrotoxicity, which limits their long-term utility. In order to understand the mechanisms of the toxicity, we analyzed the gene expression changes that underlie the development of CI immunosuppressant-mediated nephrotoxicity, in male Sprague-Dawley (SD) rats dosed daily with cyclosporine (CsA), FK506 or rapamycin (Rapa) for 1 to 28 days. We identified a group of genes, whose expression in rat kidney is quantitatively correlated with CI-induced kidney injury as observed in changes in blood urea nitrogen (BUN) levels and kidney histopathology. These genes include both up-regulated genes, such as Ren1 and Klks3, and down-regulated genes, such as Calb1, Egf, NCC, and kidney specific Wnk1 (KS-Wnk1). Using the down-regulated genes alone we successfully predicted CI immunosuppressant-mediated kidney injury in rats following 7 days of treatment. Among these genes are two mechanism-related genes, NCC and KS-Wnk1, both of which are involved in the sodium transport in the distal nephrons. The down-regulation of both genes at the mRNA and protein level in rat kidney following CI treatment was confirmed by quantitative RT-PCR and immunohistochemical staining, respectively. We hypothesize that decreased expression of NCC may cause reduced sodium chloride reabsorption in the distal tubules, and contribute to the prolonged activation of the Renin-Angiotensin-System (RAS), a demonstrated contributor to the development of CI-induced nephrotoxicity in both animal models and clinical settings. Therefore, NCC and KS-Wnk1 could potentially be used as biomarkers for early detection and prevention of CI-related nephrotoxicity in clinical practice.
Genomic-derived markers for early detection of calcineurin inhibitor immunosuppressant-mediated nephrotoxicity.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation.
Specimen part, Cell line
View SamplesOur laboratory has recently discovered that E. coli cells starved for the DNA precursor dGTP are killed efficiently (dGTP starvation) in a manner similar to that described for Thymineless Death (TLD). Conditions for specific dGTP starvation can be achieved by depriving an E. coli optA1 gpt strain of the purine nucleotide precursor hypoxanthine (Hx). To gain insight into the mechanisms underlying dGTP starvation, we conducted genome-wide gene expression analyses on actively growing optA1 gpt strains subjected to hypoxanthine deprivation for increasing periods of time. The data show that, upon Hx withdrawal, the optA1 gpt strain displays a diminished ability to de-repress the de novo purine biosynthesis genes, and this is likely due to internal guanine accumulation. The impairment to fully induce the purR regulon may be a contributing factor to the lethality of dGTP starvation. At later time points, and coinciding with cell lethality, strong induction of the SOS is observed, supporting the concept of replication stress as a final cause of death. No evidence was observed for the participation of other stress responses, including the rpoS-mediated global stress response in the starved cells, and reinforcing the lack of feedback of replication stress into the global metabolism of the cell. The genome-wide expression data also provide direct evidence for increased genome complexity during dGTP starvation, as a markedly increased gradient is observed for expression of genes located nearby the replication origin relative to those located towards the replication terminus.
Transcriptome Analysis of Escherichia coli during dGTP Starvation.
No sample metadata fields
View SamplesTo identify liver transcripts differentially expressed due to treatment with N, N-dimethyl-p-toluidine (DMPT) and p-toluidine, we collected RNA during the from male F344/N rats exposed to 0, 1, 6, 20, 60 or 120 mg/kg DMPT (or p-toluidine), 5 days after exposure for animals 5-6 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip Array.
Hepatic transcriptomic alterations for N,N-dimethyl-p-toluidine (DMPT) and p-toluidine after 5-day exposure in rats.
Specimen part
View SamplesTristetraprolin (TTP) is a tandem CCCH zinc finger protein that was identified through its rapid induction by mitogens in fibroblasts. Studies of TTP-deficient mice, and cells derived from them, showed that TTP could bind to certain AU-rich elements in mRNAs, leading to increases in the rates of mRNA deadenylation and destruction. Known physiological target
Novel mRNA targets for tristetraprolin (TTP) identified by global analysis of stabilized transcripts in TTP-deficient fibroblasts.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Revealing a human p53 universe.
Specimen part, Subject
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