Comparative analysis of mouse cardiac left ventricle gene expression: voluntary wheel exercise and pregnancy-induced cardiac hypertrophy
Distinct cardiac transcriptional profiles defining pregnancy and exercise.
Sex, Specimen part
View SamplesGenome-wide expression analysis comparison with and without ionizing radiation in p53 mutant and wild type Drosophila larvae
Genome-wide expression analysis identifies a modulator of ionizing radiation-induced p53-independent apoptosis in Drosophila melanogaster.
Sex, Specimen part, Treatment
View SamplesExpression data from valvular interstitial cells cultured in 2D or 3D PEG hydrogel systems compared to culture on tissue culture polystyrene and freshly isolated cells
Transcriptional profiles of valvular interstitial cells cultured on tissue culture polystyrene, on 2D hydrogels, or within 3D hydrogels.
Specimen part
View SamplesThe Mediator complex allows communication between transcription factors and RNA polymerase II (RNAPII). CDK8, the kinase found in some variants of Mediator, has been characterized mostly as a transcriptional repressor. Recently, CDK8 was demonstrated to be a potent oncoprotein. Here we show that CDK8 is predominantly a positive regulator of gene expression within the serum response network, as it is required for expression of several members of the AP-1 and EGR family of oncogenic transcription factors (e.g. FOS, JUN, EGR1-3). Mechanistic studies demonstrate that CDK8 is not required for recruitment of RNAPII and promoter escape at these loci. Instead, CDK8 depletion leads to the appearance of slower elongation complexes carrying hypophosphorylated RNAPII. We show that CDK8-Mediator regulates precise steps in the assembly of a functional elongation complex, including the recruitment of P-TEFb and BRD4, but is dispensable for recruitment of SPT5 and FACT. Furthermore, CDK8-Mediator specifically interacts with P-TEFb. Thus, we uncovered a novel role for CDK8 in transcriptional regulation that may contribute to its oncogenic effects.
CDK8 is a positive regulator of transcriptional elongation within the serum response network.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Anti-inflammatory properties of alpha- and gamma-tocopherol.
Sex
View SamplesThe perception that soy food products and dietary supplements will have beneficial effects on heart health has led to a massive consumer market. However, we have previously noted that diet has a profound effect on disease progression in a genetic model of hypertrophic cardiomyopathy (HCM). In this model, a soy-based diet negatively impacts cardiac function in male mice.
Remodeling the cardiac transcriptional landscape with diet.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sex, Specimen part, Treatment
View SamplesWe established the transcriptional profile of brain aging and examine the global effects of vitamin E supplementation on age-related alterations in expression in the aged mouse brain.
Anti-inflammatory properties of alpha- and gamma-tocopherol.
Sex
View SamplesTo investigate the global effects of vitamin E supplementation on heart aging, we used high-density oligonucleotide arrays to measure transcriptional alterations in 30-month-old B6C3F1 mice supplemented with - and -tocopherol since middle age (15 months).
Anti-inflammatory properties of alpha- and gamma-tocopherol.
Sex
View SamplesThis study is to find the cellular and molecular mechanisms by which a naturally-occurring Np53 isoform causes accelerated aging in humans. The biological function of Np53, which lacks only 40 N-terminal amino acids, represents an example of p53 as a regulator of mammalian aging. When expressed together with WTp53 in mice, Np53 causes an aging phenotype such as shorter life span, reduced body mass, organ atrophy and osteoporosis. Because p53 must form a tetramer to regulate transcription, we generated p53 clones (based upon the structure of the native p53 tetramer) containing one Np53 linked with one WTp53 to form a functional Np53:WTp53 tetramer with 1:1 stoichiometry. Thus, our strategy ensured each p53 tetramer contained 2 Np53 and 2 WTp53 proteins. Importantly, Np53:WTp53 form stable tetramers, based upon gel filtration chromatography and structural analysis using electron microscopy. Furthermore, the Np53:WTp53 tetramer activates transcription equally well compared with WTp53 tetramers in an in vitro reconstituted transcription system. Having verified the stoichiometry, stability, structure, and activity of these Np53:WTp53 tetramers, here we used microarray analysis to compare global gene expression patterns in p53-null H1299 cells expressing either WTp53 or Np53:WTp53. As expected, global gene expression was largely similar, since the differences between Np53:WTp53 tetramers and WTp53 tetramers are slight: only 2 of 4 p53 proteins will be different in the Np53:WTp53 tetramer. Among only several dozen genes that were selectively up- or down-regulated 2-fold or greater, many genes known to regulate mammalian aging were altered in cells expressing Np53:WTp53, including insulin signaling pathway members (IRS1, INPP5D, PLK3, MAP3K1, FGF5) and regulators of glucose metabolism (SLC2A2, CRYAB, LRCH1). Expression of other key metabolic genes were also altered in cells expressing Np53:WTp53 tetramers, suggesting that global me tabolic changes might contribute to Np53:WTp53 pathology. In collaboration with Metabolon (Durham, NC), we identified approximately one hundred metabolites that were significantly up- or down-regulated in H1299 cells expressing Np53:WTp53. The metabolome analysis was a powerful complement to the gene expression data, and further suggested that the mTOR pathway (e.g. across-the-board up-regulation of amino acid levels) and mitochondrial function (e.g. up-regulation of carnitine, important for a-oxidation of fatty acids) was altered in cells expressing Np53:WTp53. These findings were subsequently validated using biochemical and cell-based approaches. Furthermore, whereas equal expression of Np53 and WTp53 cause accelerated aging in mammals, due to alternative splicing and translation initiation Np53 is a naturally-occurring isoform whose expression levels can change throughout the lifetime. Thus, the cellular and molecular mechanisms identified from this work will likely reflect changes common to normal, physiological aging.
The human ΔNp53 isoform triggers metabolic and gene expression changes that activate mTOR and alter mitochondrial function.
Specimen part, Cell line
View Samples