Show simple item record

dc.contributor.authorThomson, John Pen
dc.contributor.authorLempiäinen, Harrien
dc.contributor.authorHackett, Jamieen
dc.contributor.authorNestor, Colm Een
dc.contributor.authorMüller, Arneen
dc.contributor.authorBolognani, Federicoen
dc.contributor.authorOakeley, Edward Jen
dc.contributor.authorSchübeler, Dirken
dc.contributor.authorTerranova, Rémien
dc.contributor.authorReinhardt, Dianaen
dc.contributor.authorMoggs, Jonathan Gen
dc.contributor.authorMeehan, Richard Ren
dc.date.accessioned2012-10-03T19:12:44Z
dc.date.available2012-10-03T19:12:44Z
dc.date.issued2012-10-03en
dc.identifier.issn1474-760X
dc.identifier.urihttp://www.dspace.cam.ac.uk/handle/1810/243849
dc.description.abstractAbstract 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.
dc.languageEnglishen
dc.language.isoen
dc.titleNon-genotoxic carcinogen exposure induces defined changes in the 5-hydroxymethylomeen
dc.typeArticle
dc.date.updated2012-10-03T19:12:44Z
dc.description.versionRIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.en
dc.rights.holderJohn P Thomson et al.; licensee BioMed Central Ltd.
prism.publicationDate2012en
dcterms.dateAccepted2012-10-03en
rioxxterms.versionofrecord10.1186/gb-2012-13-10-r93en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2012-10-03en
dc.contributor.orcidHackett, Jamie [0000-0002-6237-3684]
dc.identifier.eissn1474-760X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (092096/Z/10/Z)


Files in this item

Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record