Aging and alcohol interact to alter hepatic DNA hydroxymethylation.
Aging and alcohol interact to alter hepatic DNA hydroxymethylation.
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DOI：
10.1111/acer.12477
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Choi SW
中科院分区：
文献类型：
--
作者：
Tammen SA;Dolnikowski GG;Ausman LM;Liu Z;Sauer J;Friso S;Choi SW
衰老和长期饮酒都是DNA甲基化的修饰剂，但目前尚不清楚长期饮酒是否也会改变DNA羟甲基化，这是一种新发现的由甲基胞嘧啶氧化产生的表观遗传标记。此外，还没有测试老化和酒精是否相互作用以改变这种表观遗传现象，从而对基因表达产生独立影响。老年（18个月）和年轻（4个月）的雄性C57 BL/6小鼠配对喂食含酒精（18%的能量）的Lieber-DeCarli流质饮食或等热量Lieber-DeCarli对照饮食5周。使用新的LC/MS-MS方法分析肝脏DNA的整体DNA羟甲基化和DNA甲基化。通过qRTPCR测量泰特酶和Cyp 2 e1的肝脏mRNA表达。在年轻小鼠中，与对照小鼠相比，轻度慢性酒精暴露显著降低了整体DNA羟甲基化（0.22%±0.01% vs 0.29± 0.06%，p = 0.004）。酒精没有显着改变老年小鼠的羟甲基胞嘧啶水平。与喂食对照饮食的年轻小鼠相比，喂食对照饮食的老年小鼠显示出降低的总体DNA羟甲基化（0.24±0.02%对0.29± 0.06%，p = 0.04）。该模型表明衰老和酒精在决定DNA羟甲基化中的相互作用（pinteraction = 0.009）。Tet 2和Tet 3酶的表达在老年小鼠中相对于年轻小鼠降低（p < 0.005）。酒精改变DNA羟甲基化的观察表明酒精的一种新的表观遗传效应。这是第一个证明慢性饮酒和衰老对DNA羟甲基化的相互作用的研究。
Aging and chronic alcohol consumption are both modifiers of DNA methylation but it is not yet known whether chronic alcohol consumption also alters DNA hydroxymethylation, a newly discovered epigenetic mark produced by oxidation of methylcytosine. Furthermore, it has not been tested whether aging and alcohol interact to modify this epigenetic phenomenon, thereby having an independent effect on gene expression. Old (18 months) and young (4 months) male C57BL/6 mice were pair-fed either a Lieber-DeCarli liquid diet with alcohol (18% of energy) or an isocaloricLieber-DeCarli control diet for 5 weeks. Global DNA hydroxymethylation and DNA methylation were analyzed from hepatic DNA using a new LC/MS-MS method. Hepatic mRNA expression of the Tet enzymes and Cyp2e1 were measured via qRTPCR. In young mice, mild chronic alcohol exposure significantly reduced global DNA hydroxymethylation compared with control mice (0.22%±0.01% vs 0.29±0.06%, p = 0.004). Alcohol did not significantly alter hydroxymethylcytosine levels in old mice. Old mice fed the control diet showed decreased global DNA hydroxymethylation compared with young mice fed the control diet (0.24±0.02% vs 0.29±0.06%, p = 0.04). This model suggests an interaction between aging and alcohol in determining DNA hydroxymethylation (pinteraction = 0.009). Expression of Tet2 and Tet3 enzymes was decreased in the old mice relative to the young (p < 0.005). The observation that alcohol alters DNA hydroxymethylation indicates a new epigenetic effect of alcohol. This is the first study demonstrating the interactive effects of chronic alcohol consumption and aging on DNA hydroxymethylation.
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