Unknown

Dataset Information

0

Non-genotoxic carcinogen exposure induces defined changes in the 5-hydroxymethylome.


ABSTRACT: BACKGROUND:Induction and promotion of liver cancer by exposure to non-genotoxic carcinogens coincides with epigenetic perturbations, including specific changes in DNA methylation. Here we investigate the genome-wide dynamics of 5-hydroxymethylcytosine (5hmC) as a likely intermediate of 5-methylcytosine (5mC) demethylation in a DNA methylation reprogramming pathway. We use a rodent model of non-genotoxic carcinogen exposure using the drug phenobarbital. RESULTS:Exposure to phenobarbital results in dynamic and reciprocal changes to the 5mC/5hmC patterns over the promoter regions of a cohort of genes that are transcriptionally upregulated. This reprogramming of 5mC/5hmC coincides with characteristic changes in the histone marks H3K4me2, H3K27me3 and H3K36me3. Quantitative analysis of phenobarbital-induced genes that are involved in xenobiotic metabolism reveals that both DNA modifications are lost at the transcription start site, while there is a reciprocal relationship between increasing levels of 5hmC and loss of 5mC at regions immediately adjacent to core promoters. CONCLUSIONS:Collectively, these experiments support the hypothesis that 5hmC is a potential intermediate in a demethylation pathway and reveal precise perturbations of the mouse liver DNA methylome and hydroxymethylome upon exposure to a rodent hepatocarcinogen.

SUBMITTER: Thomson JP 

PROVIDER: S-EPMC3491421 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications


<h4>Background</h4>Induction and promotion of liver cancer by exposure to non-genotoxic carcinogens coincides with epigenetic perturbations, including specific changes in DNA methylation. Here we investigate the genome-wide dynamics of 5-hydroxymethylcytosine (5hmC) as a likely intermediate of 5-methylcytosine (5mC) demethylation in a DNA methylation reprogramming pathway. We use a rodent model of non-genotoxic carcinogen exposure using the drug phenobarbital.<h4>Results</h4>Exposure to phenobar  ...[more]

Similar Datasets

2012-09-12 | GSE40773 | GEO
2012-09-12 | E-GEOD-40773 | biostudies-arrayexpress
2013-03-25 | GSE45465 | GEO
2015-05-18 | GSE57129 | GEO
2015-05-18 | GSE57082 | GEO
| S-EPMC8396440 | biostudies-literature
2013-03-25 | E-GEOD-45465 | biostudies-arrayexpress
2015-05-18 | E-GEOD-57082 | biostudies-arrayexpress
2015-05-18 | E-GEOD-57129 | biostudies-arrayexpress
| S-EPMC4804129 | biostudies-literature