Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate/methyl-deficient diet
Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate/methyl-deficient diet
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DOI：
10.1016/j.brainres.2008.07.077
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发表时间：
2008-10-27
期刊：
影响因子：
2.9
通讯作者：
Tryndyak, Volodymyr P.
中科院分区：
文献类型：
--
作者：
Pogribny, Igor P.;Karpf, Adam R.;Tryndyak, Volodymyr P.
细胞表观基因组景观的维持取决于一碳代谢途径的状态，对于正常的中枢神经系统发育和功能至关重要。在本研究中，我们研究了Fisher 344大鼠大脑中的表观遗传学改变，这些大鼠长期摄入缺乏必需的一碳营养素、蛋氨酸、胆碱和叶酸的饮食。结果表明，喂养叶酸/甲基缺乏的饮食会导致整体DNA超甲基化，如基因组5-甲基-2 '-脱氧胞苷（5 mdC）含量增加所示，更重要的是，未甲基化的富含CpG的DNA结构域中甲基化的增加。有趣的是，这些表观遗传变化与在同一叶酸/甲基缺乏大鼠的肝脏中观察到的变化相反。超甲基化变化与从头DNA甲基转移酶DNMT 3a和甲基-CpG结合蛋白2的蛋白表达增加相关。此外，基因表达谱鉴定了33个显著上调或下调的基因（倍数变化> 1.5和p
The maintenance of the cellular epigenomic landscape, which depends on the status of the one-carbon metabolic pathway, is essential for normal central nervous system development and function. In the present study, we examined the epigenetic alterations in the brains of Fisher 344 rats induced by the long-term administration of a diet lacking of essential one-carbon nutrients, methionine, choline, and folic acid. The results demonstrated that feeding a folate/methyl-deficient diet causes global DNA hypermethylation as indicated by an increase of genomic 5-methyl-2'-deoxycytidine (5mdC) content and more importantly, by an increase of methylation within unmethylated CpG-rich DNA domains. Interestingly, these epigenetic changes were opposite to those observed in the livers of the same folate/methyl-deficient rats. The hypermethylation changes were associated with an increased protein expression of de novo DNA methyltransferase DNMT3a and methyl-CpG-binding protein 2. Additionally, the gene expression profiling identified 33 significantly up- or down-regulated genes (fold change > 1.5 and p