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.
Direct targets of CodY in Staphylococcus aureus.
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View SamplesPKR is an interferon induced serine/threonine protein kinase, that is activated by double stranded RNA. PKR plays an important role in the antiviral defense by interferon. In addition to its role in translation, PKR participates in several signaling pathways to transcription. The goal of this experiment is to study the role of PKR in regulating gene expression in our NIH 3T3 inducible cell line, which could overexpress PKR wt protein after the removal of tetracycline (Donze O, Dostie J, Sonenberg N. (1999) Virology 256: 322-9).
The protein kinase PKR: a molecular clock that sequentially activates survival and death programs.
Cell line
View SamplesReduced cancer incidence has been reported among type II diabetics treated with metformin. Metformin exhibits anti-proliferative and anti-neoplastic effects associated with inhibition of mTORC1, but the mechanisms are poorly understood. We provide the first genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) and metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Importantly, metformin's anti-proliferative activity can be explained by selective translational suppression of mRNAs encoding cell cycle regulators via the mTORC1/4E-BP pathway. Thus, metformin selectively inhibits mRNA translation of encoded proteins that promote neoplastic proliferation, motivating further studies of this compound and related biguanides in cancer prevention and treatment.
Distinct perturbation of the translatome by the antidiabetic drug metformin.
Cell line, Treatment
View SamplesTranslation is a critical cellular process to synthesize proteins from their transcripts. However, translational regulation in antigen-specific T cells in vivo has not been well defined.
Translation is actively regulated during the differentiation of CD8<sup>+</sup> effector T cells.
Sex, Specimen part
View SamplesWe analysed whole PolyA+ RNA from human osteosarcoma U2OS cells depleted for human Cactin or transfected with a control shRNA. Overall design: Two independent shRNAs targeting human Cactin (shCac_C and shCac_D), a control shRNA (shCtrl), a single cell line (U2OS)
Human cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion.
Cell line, Treatment, Subject, Time
View SamplesTo characterize the potential molecular pathway(s) affected by iron treatment and identify the one(s) responsible for C3 induction, we performed a whole genome microarray on untreated ARPE-19 cells and cells treated with 250 M FAC for 48h/2d.
Iron-induced Local Complement Component 3 (C3) Up-regulation via Non-canonical Transforming Growth Factor (TGF)-β Signaling in the Retinal Pigment Epithelium.
Cell line, Treatment
View SamplesBPH/5 mice are an inbred strain with “borderline hypertension” that spontaneously develops both maternal and fetal hallmarks of preeclampsia. RNA-Seq analysis of BPH/5 uterine implantation sites at embryonic day 7.5, the peak of decidualization, identifies differential expression of inflammatory response genes, including members of the complement family, compared to C57 controls. Overall design: RNA-Seq was performed on RNA isolated from E7.5 BPH/5 and C57 implantation sites (n=4).
Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.
Cell line, Subject
View SamplesOne current focus of nutrition research is the identification of biomarkers that reflect the impact of food on metabolic processes. As this approach mostly targets the prevention rather than the curing of diseases, novel biomarkers need to be identified. Those should be influenced by the diet already in healthy individuals and be nonetheless indicative, or even predictive, of the potential impact of specific food on the development of metabolic diseases such as obesity.
Caloric dose-responsive genes in blood cells differentiate the metabolic status of obese men.
Specimen part
View SamplesTo identify the genes whose expression levels are changed before and after somatic cell reprogramming, we performed global gene expression analysis of iPS cells and their original fibrobrasts.
Structural and spatial chromatin features at developmental gene loci in human pluripotent stem cells.
Specimen part, Cell line
View SamplesTime course micro array experiment to identify transcriptional changes in response to exposure of hFLs to different combinations of small molecules during direct neuronal reprogramming
Small molecules increase direct neural conversion of human fibroblasts.
Specimen part, Treatment, Time
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