ArticlePloS one2011
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 85 citations in OpenAlex.
- Gut microbiota trigger host liver immune responses that affect drug-metabolising enzymes.Frontiers in immunology · 2024Review
- Epigenetic Mechanisms Contribute to Intraindividual Variations of Drug Metabolism Mediated by Cytochrome P450 Enzymes.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Unboxing the molecular modalities of mutagens in cancer.Environmental science and pollution research international · 2022Review
- Impact of Neonatal Activation of Nuclear Receptor CAR (Nr1i3) on Cyp2 Gene Expression in Adult Mouse Liver.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain.Annual review of pharmacology and toxicology · 2021Review
- smORFunction: a tool for predicting functions of small open reading frames and microproteins.BMC bioinformatics · 2020Article
- Early microRNA indicators of PPARα pathway activation in the liver.Toxicology reports · 2020Article
- Drug-induced chromatin accessibility changes associate with sensitivity to liver tumor promotion.Life science alliance · 2019Article
- Chromatin dynamics underlying latent responses to xenobiotics.Toxicology research · 2018Review
- Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations.Genome biology · 2018Article
- Defining baseline epigenetic landscapes in the rat liver.Epigenomics · 2017Article
- Candidate genes responsible for early key events of phenobarbital-promoted mouse hepatocellular tumorigenesis based on differentiation of regulating genes between wild type mice and humanized chimeric mice.Toxicology research · 2017Article
- Incorporation of an Epigenetic Evaluation into Safety Assessment: What we First Need to Know.Current opinion in toxicology · 2017Article
- Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via Tdg in the mouse liver.Scientific reports · 2016Article
- RNA-Seq reveals common and unique PXR- and CAR-target gene signatures in the mouse liver transcriptome.Biochimica et biophysica acta · 2016Article
- Loss of Tet1-Associated 5-Hydroxymethylcytosine Is Concomitant with Aberrant Promoter Hypermethylation in Liver Cancer.Cancer research · 2016Article
- Evidence that the capacity of nongenotoxic carcinogens to induce oxidative stress is subject to marked variability.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- Association of childhood chronic physical aggression with a DNA methylation signature in adult human T cells.PloS one · 2014Article
- The roles of co-chaperone CCRP/DNAJC7 in Cyp2b10 gene activation and steatosis development in mouse livers.PloS one · 2014Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evidence 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.