Early nutrition affects adult metabolism in humans and other mammals, potentially via persistent alterations in DNA methylation. With viable yellow agouti (Avy) mice, which harbor a transposable element in the agouti gene, we tested the hypothesis that the metastable methylation status of specific transposable element insertion sites renders them epigenetically labile to early methyl donor nutrition. Our results show that dietary methyl supplementation of a/a dams with extra folic acid, vitamin B12, choline, and betaine alter the phenotype of their Avy/a offspring via increased CpG methylation at the Avy locus and that the epigenetic metastability which confers this lability is due to the Avy transposable element. These findings suggest that dietary supplementation, long presumed to be purely beneficial, may have unintended deleterious influences on the establishment of epigenetic gene regulation in humans.
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机译：早期营养可能会通过DNA甲基化的持续改变而影响人类和其他哺乳动物的成年代谢。对于在 agouti 基因中带有转座因子的可行的黄色刺豚鼠（ A vy ）小鼠，我们检验了亚稳态甲基化状态的假设特定转座因子插入位点的数量使得它们对早期甲基供体营养表观遗传不稳定。我们的结果表明，膳食中补充额外叶酸，维生素B 12 ，胆碱和甜菜碱的 a / a 大坝会改变其 A vy / a 后代通过在 A vy 位点增加CpG甲基化而赋予这种不稳定性的表观遗传亚稳态是由于< em> A vy 转座元素。这些发现表明，长期以来人们认为膳食补充剂完全是有益的，它可能对人类表观遗传基因调控的建立产生意想不到的有害影响。
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