Germ-line epigenetic modification of the murine Avy allele by nutritional supplementation
Germ-line epigenetic modification of the murine Avy allele by nutritional supplementation
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DOI：
10.1073/pnas.0607090103
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发表时间：
2006-11-14
影响因子：
11.1
通讯作者：
Martin, David I. K.
中科院分区：
文献类型：
--
作者：
Cropley, Jennifer E.;Suter, Catherine M.;Martin, David I. K.
表观遗传修饰可以介导环境对表型的影响。小鼠A（vy）等位基因的表观遗传状态是高度可变的，并且决定表型。这些效应在马赛克谱中变化，可以通过子宫内暴露于甲基供体补充而改变。我们已经询问了甲基供体补充是否影响A（vy）等位基因的生殖系表观遗传状态。我们发现，体细胞表观遗传状态的A（vy）的影响，在子宫内甲基供体补充只有当等位基因是父系贡献。在妊娠中期暴露于甲基供体补充剂不仅在胎儿暴露的小鼠中改变了A（vy）表型，而且在其后代中也改变了A（vy）表型。这一发现表明，甲基供体可以改变生殖系中A（vy）等位基因的表观遗传状态，并且通过配子发生和胚胎发生中发生的表观遗传重置保留改变的状态。因此，母亲的饮食可能会对后代产生持久的影响，而不受后来饮食变化的影响。虽然其他报告已经提出了这种可遗传的表观遗传变化，这项研究表明，一个特定的哺乳动物基因可以受到生殖系表观遗传变化。
Environmental effects on phenotype can be mediated by epigenetic modifications. The epigenetic state of the murine A(vy) allele is highly variable, and determines phenotypic. effects that vary in a mosaic spectrum that can be shifted by in utero exposure to methyl donor supplementation. We have asked if methyl donor supplementation affects the germ-line epigenetic state of the A(vy) allele. We find that the somatic epigenetic state of A(vy) is affected by in utero methyl donor supplementation only when the allele is paternally contributed. Exposure to methyl donor supplementation during midgestation shifts A(vy) phenotypes not only in the mice exposed as fetuses, but in their offspring. This finding indicates that methyl donors can change the epigenetic state of the A(vy) allele in the germ line, and that the altered state is retained through the epigenetic resetting that takes place in gametogenesis and embryogenesis. Thus a mother's diet may have an enduring influence on succeeding generations, independent of later changes in diet. Although other reports have suggested such heritable epigenetic changes, this study demonstrates that a specific mammalian gene can be subjected to germ-line epigenetic change.