This SuperSeries is composed of the SubSeries listed below.
Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle.
Sex, Specimen part
View SamplesTo define the direct gene expression changes in normal human skeletal muscle with mineralocorticoid and glucocorticoid receptor agonist and antagonist treatment.
Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle.
Sex, Specimen part
View SamplesTo uncover whether aldosterone induces gene expression changes through mineralocorticoid or glucocorticoid receptors and determine if eplerenone and spironolactone could block aldosterone induced gene expression to the same extent
Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle.
Sex, Specimen part
View SamplesThe mineralocorticoid aldosterone mainly produced by the adrenal gland is essential for life but an abnormal excessive secretion causes severe pathological effects including hypertension and target organ injury in the heart and kidney. The aim of this study was to determine the gene regulatory network triggered by aldosterone secretagogues in a non transformed cell system. Freshly isolated rat adrenal zona glomerulosa cells were stimulated with the two main aldosterone secretagogues, angiotensin II and potassium, for two hours and subjected to whole genome expression studies using multiple biological and bioinformatics tools. Several genes were differentially expressed by Ang II (n=133) or potassium (n=216). Genes belonging to the nucleic acid binding and transcription factor activity categories were significantly enriched. A subset of the most regulated genes were confirmed by real-time RT-PCR and then their expression analyzed in time curve studies. Differentially expressed genes were grouped according to their time-response expression pattern and their promoter regions analyzed for common regulatory transcription factors binding sites. Finally, data mining with gene promoters, transcription factors and literature databases were performed to generate gene interaction networks for either Ang II or potassium. This study provides for the first time a complete study of the genes that are regulated, and the interaction between them, by aldosterone secretagogues in rat adrenal cells. Increasing our knowledge of adrenal physiology and gene regulation in non transformed cell systems would lead us to a better approach for discovery of candidate genes involved pathological conditions of the adrenal cortex.
Gene expression profile in rat adrenal zona glomerulosa cells stimulated with aldosterone secretagogues.
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View SamplesTo test for a function effect of mineralocorticoid receptor modulation in skeletal muscle, global gene expression analysis was conducted on human myltubes treated with a mineralocorticoid receptor agonist or antagonist.
Mineralocorticoid receptors are present in skeletal muscle and represent a potential therapeutic target.
Sex
View SamplesTo identify the gene expression differences in skeletal muscles resulting from treatment of dystrophic mice with spironolactone plus lisinopril
Mineralocorticoid receptors are present in skeletal muscle and represent a potential therapeutic target.
Sex, Age, Treatment
View SamplesDREAM (downstream regulatory element antagonist modulator) is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. Previous studies have shown a role for DREAM in cerebellar function regulating the expression of the sodium/calcium exchanger3 (NCX3) in cerebellar granules to control Ca2+ homeostasis and survival of these neurons. To achieve a more global view of the genes regulated by DREAM in the cerebellum, we performed a genome-wide analysis in transgenic cerebellum expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Our results indicate that DREAM is a major transcription factor in the cerebellum that regulates genes important for cerebellar development.
Reduced Mid1 Expression and Delayed Neuromotor Development in daDREAM Transgenic Mice.
Specimen part
View SamplesPURPOSE
Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer.
Specimen part, Disease
View SamplesAnalysis of chromatin architecture suggests that the 3D structure of the genome plays a major role in regulating gene expression, orchestrating the compartmentalization of chromatin and facilitating specific enhancer-promoter interactions. However, the mechanisms that control this structuring of the genome are not fully understood. We have addressed this issue by analyzing the role of CTCF, a major architectural factor in chromatin structure, in the embryonic heart. Loss of CTCF triggered an overall downregulation of the cardiac developmental program, suggesting that CTCF facilitates enhancer-promoter interactions in the developing heart. Detailed analysis of the IrxA gene cluster showed that CTCF loss leads to disruption of the heart-specific regulatory domain that surrounds Irx4, resulting in changes in expression of IrxA cluster genes and neighboring genes. In contrast to the critical role proposed for CTCF in organizing large-scale chromatin domains, our results show that CTCF preferentially mediates local regulatory interactions. Overall design: RNAseq of mouse embryonic E10.5 hearts in three conditions: 1) control (labeled as WT), 2) heterozygous (labeled as HET) and 3) homozygous (labeled as KO). Three replicates were performed for each condition, each consisting of a pool of 6 hearts. Tissue was mechanically disaggregated and RNA extracted with trizol and purified through columns.
CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart.
Specimen part, Cell line, Subject
View SamplesChanges in nuclear Ca2+ homeostasis activate specific gene expression programs and are central to the acquisition and the plastic storage of memories. DREAM /KChIP proteins form heterotetramers that bind DNA and repress transcription in a Ca2+-dependent manner. Single ablation of one member of the DREAM/KChIP family may result in a mild or the absence of phenotype due to partial gene compensation. To study the function of DREAM/KChIP proteins in the brain, we used transgenic mice expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). We show that daDREAM controls the expression of several activity-dependent transcription factors including Npas4, Nr4a1, Mef2C, JunB and c-Fos, as well as the chromatin modifying enzyme Mbd4 and proteins related to actin polymerization like Arc and gelsolin. Thus, directly or through these targets, expression of daDREAM in the forebrain resulted in a complex phenotype characterized by i) impaired learning and memory, ii) loss of recurrent inhibition and enhanced LTP in the dentate gyrus without affecting Kv4-mediated potassium currents, and iii) modified spine density in DG granule neurons. Our results propose DREAM as a master-switch transcription factor regulating several activity-dependent gene expression programs to control synaptic plasticity, learning and memory.
DREAM controls the on/off switch of specific activity-dependent transcription pathways.
Specimen part
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