This SuperSeries is composed of the SubSeries listed below.
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sex, Specimen part, Treatment, Time
View SamplesDynamic changes in the mouse liver DNA methylome associated with short (1 day) and prolonged (7, 28 and 91 days) exposure to the rodent liver non-genotoxic carcinogen (NGC), phenobarbital (PB).
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Specimen part, Treatment
View Samples29-32 days old male mice where either treated with Phenobarbital or untreated
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sex, Specimen part, Treatment, Time
View SamplesWe report the genome-wide RNA expression levels in pluripotent mESC and as mESC differentiate towards a neuronal lineage in response to high levels of Retinoic Acid treatment in vitro. RNA-seq was performed to identify all RNAs expressed in both ESCs and neuronal cells. In total, In total, 14,443 expressed genes were detected, of which 1,834 were up-regulated and 1,477 down-regulated (fold change (FC) > -/+2.0 and p-value < 0.035) during RA-induced neuronal differentiation. The top down-regulated genes included members of the pluripotency core transcriptional network, including Klf4, Sox2, Oct4, Nanog, Suz12, Esrrb, Stat3 and Tcfcp2l1. The top up-regulated genes are important for neuronal differentiation (e.g. Pax3, Irx3, Rest and Foxd3) and reside in the RA-pathway (e.g. various homeobox genes), the retinoic acid receptors and the RA-degradation enzyme Cyp26a1. Overall design: Examination, identification and comparision of mRNA expression profliles in two cellular states.
Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1).
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Age, Specimen part, Treatment, Subject, Time
View SamplesThe carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. For insight into early mechanisms of non-genotoxoc carcinogenesis and for identification of potential early biomarkers of non-genotoxic carcinogenesis, groups of rats were treated with a range of known non-genotoxic carcinogens for a period of 14, 28, or 90 days, and liver tissue was harvested for expression profiling. Control groups were treated with appropriate vehicles.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Specimen part, Treatment, Subject
View SamplesConventional notion regards the action of non-genotoxic carcinogens (NGC) an autonomous process largely confined to parenchymal cells. Here we aim to elucidate the role of the hepatic mesenchyme for the action of two prototypical NGC, phenobarbital (PB), an anti-epileptic drug, and cyproterone acetate (CPA) a gestagen used in contraceptive pills.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Specimen part, Treatment
View SamplesHere we investigate the difference in global gene expression in different tumor types found in the liver of rats after NNM-initiation/PB-promotion of tumor growth. We aim to identify tumor characteristic expression in nodules, focii, adenomas and carcinomas.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Specimen part, Treatment
View SamplesEvidence suggests that epigenetic perturbations are involved in the adverse effects associated with some drugs and toxicants, including certain classes of non-genotoxic carcinogens. Such epigenetic changes (altered DNA methylation and covalent histone modifications) may take place at the earliest stages of carcinogenesis and their identification holds great promise for biomedical research. Here, we evaluate the sensitivity and specificity of genome-wide epigenomic and transcriptomic profiling in phenobarbital (PB)-treated B6C3F1 mice, a well-characterized rodent model of non-genotoxic liver carcinogenesis. Methylated DNA Immunoprecipitation (MeDIP)-coupled microarray profiling of 17,967 promoter regions and 4,566 intergenic CpG islands was combined with genome-wide mRNA expression profiling to identify liver tissue-specific PB-mediated DNA methylation and transcriptional alterations. Only a limited number of significant anti-correlations were observed between PB-induced transcriptional and promoter-based DNA methylation perturbations. However, the constitutive androstane receptor (CAR) target gene Cyp2b10 was found to be concomitantly hypomethylated and transcriptionally activated in a liver tissue-specific manner following PB treatment. Furthermore, analysis of active and repressive histone modifications using chromatin immunoprecipitation revealed a strong PB-mediated epigenetic switch at the Cyp2b10 promoter. Our data reveal that PB-induced transcriptional perturbations are not generally associated with broad changes in the DNA methylation status at proximal promoters and suggest that the drug-inducible CAR pathway regulates an epigenetic switch from repressive to active chromatin at the target gene Cyp2b10. This study demonstrates the utility of integrated epigenomic and transcriptomic profiling for elucidating early mechanisms and biomarkers of non-genotoxic carcinogenesis.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Specimen part, Treatment, Subject
View Samples