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Chronic alcohol consumption has greater impact on hepatic DNA hydroxymethylation in young mice relative to old
Author(s) -
Tammen Stephanie A.,
Dolnikowski Gregory G.,
Ausman Lynne M.,
Sauer Julia,
Friso Simonetta,
Choi SangWoon
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.640.15
Subject(s) - alcohol , dna methylation , alcohol consumption , epigenetics , medicine , endocrinology , dna damage , dna , chemistry , physiology , gene , biochemistry , gene expression
Aging and chronic alcohol consumption affects DNA methylation, changing gene transcription. It is not yet known whether these factors also alter DNA hydroxymethylation (hmC), an epigenetic mark produced by oxidation of methylcytosine. Our objective was to determine changes in hmC caused by aging and alcohol. Young (4 months; n=20) and old (18 months; n=18) male C57BL/6 mice were pair‐fed a Lieber‐DeCarli liquid diet with or without alcohol (18% of energy) for 5 weeks. Global hmC was analyzed from hepatic DNA using an LC/MS‐MS method and calculated as percent of total cytosine. Differentially hydroxymethylated regions (DhMRs) were determined by microarray‐based hydroxymethyl‐DNA immunoprecipitation (hmeDIP‐chip). Relative to the controls, chronic alcohol consumption did not alter global hmC in old mice, but significantly reduced global hmC in young mice (0.22%±0.01% vs 0.29±0.06%, p=0.004). Old mice had significantly lower global DNA hmC than young mice (0.24±0.02% vs 0.29±0.06%, p=0.04). This model also suggests an interaction between aging and alcohol in determining global hmC levels (p int. =0.01). Genomic hmC patterns followed a similar trend; the alcohol diet resulted in more DhMRs in young mice compared to old (431 vs 196 DhMRs). This is the first study on the effects of alcohol consumption and aging on hmC levels and posits that chronic alcohol consumption differently affects hmC in young and old mice. Grant Funding Source : NIH grant R01 AG025834