ArticleNucleic acids research2013
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 89 citations in OpenAlex.
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- 5-Hydroxymethylcytosine: Far Beyond the Intermediate of DNA Demethylation.International journal of molecular sciences · 2024Review
- TET2 regulation of alcoholic fatty liver viaiScience · 2024Article
- Inferring the Cancer Cellular Epigenome Heterogeneity via DNA Methylation Patterns.Cancer treatment and research · 2023Article
- Review
- 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
- DNA Methylation in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2020Review
- Genome-wide 5-hydroxymethylcytosine (5hmC) emerges at early stage of in vitro differentiation of a putative hepatocyte progenitor.Scientific reports · 2020Article
- Hydroxymethylation and tumors: can 5-hydroxymethylation be used as a marker for tumor diagnosis and treatment?Human genomics · 2020Review
- Environmental Epigenetics and Genome Flexibility: Focus on 5-Hydroxymethylcytosine.International journal of molecular sciences · 2020Review
- Drug-induced chromatin accessibility changes associate with sensitivity to liver tumor promotion.Life science alliance · 2019Article
- DNA Hydroxymethylation at the Interface of the Environment and Nonalcoholic Fatty Liver Disease.International journal of environmental research and public health · 2019Review
- Modelling non-alcoholic fatty liver disease in human hepatocyte-like cells.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Article
- Case examples of an evaluation of the human relevance of the pyrethroids/pyrethrins-induced liver tumours in rodents based on the mode of action.Toxicology research · 2018Review
- Chromatin dynamics underlying latent responses to xenobiotics.Toxicology research · 2018Review
- 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
- Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes.Chemical research in toxicology · 2017Article
- Cytosine 5-hydroxymethylation regulates VHL gene expression in renal clear cell carcinoma.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Aberrant DNA methylation is a common feature of neoplastic lesions, and early detection of such changes may provide powerful mechanistic insights and biomarkers for carcinogenesis. Here, we investigate dynamic 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, phenobarbital (PB). We find that the distribution of 5mC/5hmC is highly consistent between untreated individuals of a similar age; yet, changes during liver maturation in a transcriptionally dependent manner. Following drug treatment, we identify and validate a series of differentially methylated or hydroxymethylated regions: exposure results in staged transcriptional responses with distinct kinetic profiles that strongly correlate with promoter proximal region 5hmC levels. Furthermore, reciprocal changes for both 5mC and 5hmC in response to PB suggest that active demethylation may be taking place at each set of these loci via a 5hmC intermediate. Finally, we identify potential early biomarkers for non-genotoxic carcinogenesis, including several genes aberrantly expressed in liver cancer. Our work suggests that 5hmC profiling can be used as an indicator of cell states during organ maturation and drug-induced responses and provides novel epigenetic signatures for non-genotoxic carcinogen exposure.
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Registered trials
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.