This SuperSeries is composed of the SubSeries listed below.
Systematic identification of trans eQTLs as putative drivers of known disease associations.
Sex, Specimen part
View SamplesSamples were collected from 'control participants' of the Heart and Vascular Health (HVH) study that constitutes a group of population based case control studies of myocardial infarction (MI), stroke, venous thromboembolism (VTE), and atrial fibrillation (AF) conducted among 30-79 year old members of Group Health, a large integrated health care organization in Washington State.
Systematic identification of trans eQTLs as putative drivers of known disease associations.
Sex, Specimen part
View SamplesSamples were collected from 'control participants' of the Heart and Vascular Health (HVH) study that constitutes a group of population based case control studies of myocardial infarction (MI), stroke, venous thromboembolism (VTE), and atrial fibrillation (AF) conducted among 30-79 year old members of Group Health, a large integrated health care organization in Washington State.
Systematic identification of trans eQTLs as putative drivers of known disease associations.
Sex, Specimen part
View SamplesTopical corticosteroids and calcineurin inhibitors are well known treatments of atopic dermatitis (AD), but differ in their efficacy and side effects. A study in AD patients has demonstrated that betamethasone valerate (BM) though clinically more efficient impaired skin barrier repair in contrast to pimecrolimus. Objective: The present study elucidates the mode of action of topical BM and pimecrolimus cream in AD.
Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis.
Specimen part
View Samples2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces myriad toxicities in most mammals. In rodents alone, there is a huge divergence in the toxicological response across species, as well as among different strains within a species. But there are also significant differences between males and females animals of a single strain. These differences are inconsistent across model systems: the severity of toxicity is greater in female rats than males, while male mice and guinea pigs are more sensitive than females. Because the specific events that underlie this difference remain unclear, we characterized the hepatic transcriptional response of adult male and female C57BL/6 mice to 500g/kg TCDD at multiple time-points. The transcriptional profile diverged significantly between the sexes. Female mice demonstrated a large number of altered transcripts as early as 6h following treatment, suggesting a large primary response. Conversely, male animals showed the greatest TCDD-mediated response 144h following exposure, potentially implicating significant secondary responses. Nr1i3 was statistically significantly induced at all time-points in the sensitive male animals. This mRNA encodes the constitutive androstane receptor (CAR), a transcription factor involved in the regulation of xenobiotic metabolism, lipid metabolism, cell cycle and apoptosis. Surprisingly though, changes at the protein level (aside from the positive control, CYP1A1) were modest, with only FMO3 showing clear induction, and no genes with sex-differences. Thus, while male and female mice show transcriptional differences in their response to TCDD, their association with TCDD-induced toxicities remains unclear.
Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD.
Sex, Specimen part
View Samples2,3,7,8tetrachlorodibenzo-p-dixion (TCDD) is the most potent of the dioxin congeners, capable of causing a wide range of toxic effects across numerous animal models. Previous studies have demonstrated that males and females of the same species can display divergent sensitivity phenotypes to TCDD toxicities. Although it is now clear that most TCDD-induced toxic outcomes are mediated by the aryl hydrocarbon receptor (AHR), the mechanism of differential responses to TCDD exposure between sexes remains largely unknown. To investigate the differential sensitivities in male and female mice, we profiled the hepatic transcriptomic responses 4 days following exposure to various amounts of TCDD (125, 250, 500 or 1000 g/kg) in adult male and female C57BL/6Kuo mice.
Male and female mice show significant differences in hepatic transcriptomic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Sex, Specimen part
View SamplesRecently a genome of Russian individual (somatic DNA from blood) was sequenced (Skryabin et al. 2009). That study was continued to find a linkage between genetic differences in parental alleles and bias in biallelic expression of genes.
Individual genome sequencing identified a novel enhancer element in exon 7 of the CSFR1 gene by shift of expressed allele ratios.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Anti-diabetic rosiglitazone remodels the adipocyte transcriptome by redistributing transcription to PPARγ-driven enhancers.
Cell line, Treatment, Time
View SamplesThe dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a wide range of toxic effects in rodent species, all of which are mediated by a ligand-dependent transcription-factor, the aryl hydrocarbon receptor (AHR). The Han/Wistar (Kuopio) (H/W) strain shows exceptional resistance to many TCDD-induced toxicities; the LD50 of >9600 g/kg for H/W rats is higher than for any other wild-type mammal known. We have previously shown that this resistance primarily results from H/W rats expressing a variant AHR isoform that has a substantial portion of the AHR transactivation domain deleted. Despite this large deletion, H/W rats are not entirely refractory to the effects of TCDD; the variant AHR in these animals remains fully competent to up-regulate well-known dioxin-inducible genes. TCDD-sensitive (Long-Evans, L-E) and resistant (H/W) rats were treated with either corn-oil (with or without feed-restriction) or 100 g/kg TCDD for either four or ten days. Hepatic transcriptional profiling was done using microarrays, and was validated by RT-PCR analysis of 41 genes. . A core set of genes was altered in both strains at all time points tested, including CYP1A1, CYP1A2, CYP1B1, Nqo1, Aldh3a1, Tiparp, Exoc3, and Inmt. Outside this core, the strains differed significantly in the breadth of response: three-fold more genes were altered in L-E than H/W rats. At ten days almost all expressed genes were dysregulated in L-E rats, likely reflecting emerging toxic responses. Far fewer genes were affected by feed-restriction, suggesting that only a minority of the TCDD-induced changes are secondary to the wasting syndrome.
Hepatic transcriptomic responses to TCDD in dioxin-sensitive and dioxin-resistant rats during the onset of toxicity.
Sex
View SamplesRosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for PPARg, the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to the NR on DNA, explains positive regulation of gene expression, but ligand-dependent repression is not well understood. We have now addressed this issue by studying the direct effects of rosiglitazone on gene transcription, using global run-on sequencing (GRO-seq). Rosi-induced changes in gene body transcription were pronounced after 10 minutes and correlated with steady-state mRNA levels as well as with transcription at nearby enhancers (eRNAs). Upregulated eRNAs occurred almost exclusively at PPARg binding sites, to which rosi treatment recruited the coactivator MED1. By contrast, transcriptional repression by rosi involved a loss of MED1 from eRNA sites devoid of PPARg and enriched for other TFs including AP-1 factors and C/EBPs. Thus, rosi activates and represses transcription by fundamentally different mechanisms that could inform the future development of antidiabetic drugs.
Anti-diabetic rosiglitazone remodels the adipocyte transcriptome by redistributing transcription to PPARγ-driven enhancers.
Cell line, Treatment, Time
View Samples