Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases
Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases
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DOI：
10.1016/j.nut.2003.09.011
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发表时间：
2004-01-01
期刊：
影响因子：
4.4
通讯作者：
Jirtle, RL
中科院分区：
文献类型：
--
作者：
Waterland, RA;Jirtle, RL
最近对营养基因组学 1、2 这个有前景的领域进行调查的几篇评论并未讨论表观遗传机制在营养与基因组之间的联系中所发挥的重要作用。这是一个明显的遗漏。当然，人类的“营养素-基因相互作用”使各种营养素能够短暂影响特定基因子集的表达。然而，除了这些现象之外，越来越明显的是，通过与调节整个基因组区域染色质构象的表观遗传机制相互作用，关键个体发育阶段的短暂营养刺激可以对各种基因的表达产生持久影响。 3 此外，这种表观遗传变化如果发生在配子中，则可能是可遗传的。本综述重点关注早期营养对胞嘧啶甲基化的影响。它提出某些基因组区域，包括基因组印记结构域和特定转座子插入位点，特别容易受到这种影响。考虑到基因组印记基因在哺乳动物生长和发育中发挥的关键作用 4 以及我们基因组中由转座子组成的巨大比例，5 对这些基因组成分的早期营养影响可能会对人类健康产生重大影响。详细阐述了这些不同类别元素之间的基因组和表观遗传相似性，并讨论了未来研究的关键领域。
Several recent reviews surveying the promising field of nutrigenomics 1, 2 have not discussed the important role that epigenetic mechanisms play at the nexus between nutrition and the genome. This is a glaring omission. Certainly,“nutrient–gene interactions” in humans enable various nutrients to transiently influence the expression of specific subsets of genes. In addition to these phenomena, however, it is becoming increasingly evident that by interacting with epigenetic mechanisms, which regulate chromatin conformation across entire genomic regions, transient nutritional stimuli at critical ontogenic stages can wield lasting influences on the expression of various genes. 3 Moreover, such epigenetic changes, if they occur in the gametes, may be heritable. This review focuses on early nutritional influences on cytosine methylation. It proposes that certain genomic regions, including genomically imprinted domains and specific transposon insertion sites, are especially labile to such influences. Considering the critical roles that genomically imprinted genes play in mammalian growth and development 4 and the huge proportion of our genome that is comprised of transposons, 5 early nutritional influences on these genomic components could have a substantial impact on human health. Genomic and epigenetic similarities between these distinct classes of elements are elaborated, and key areas of future research are discussed.