Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice.

Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice.
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DOI:
10.1126/science.aaf7040
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发表时间:
2016-07-29
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Rakyan VK
Rakyan VK
中科院分区:
其他
文献类型:
--
作者:
Holland ML;Lowe R;Caton PW;Gemma C;Carbajosa G;Danson AF;Carpenter AA;Loche E;Ozanne SE;Rakyan VK

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次优的早期生活环境可以影响终生表型,表观遗传因素被认为是这些影响的关键媒介。我们发现,小鼠的早期蛋白质限制诱导生长限制与核糖体DNA (rDNA)特定遗传变异的DNA甲基化之间存在线性相关性,这种相关性在暴露停止后很长时间内仍然存在。在母体高脂肪或致肥性饮食模型中也发现了相关影响。我们的工作定义了基因环境诱导表观遗传动力学的一个独特的例子,并建立了rDNA作为在哺乳动物和非哺乳动物模型中发现的营养损伤的唯一已知基因组靶点。
Sub-optimal early life environments can influence life-long phenotypes, and epigenetic factors are thought to be key mediators of these effects. We show that early life protein restriction in mice induces a linear correlation between growth restriction and DNA methylation at a specific genetic variant of ribosomal DNA (rDNA), which is present long after exposure has ceased. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work defines a unique example of gene-environment induced epigenetic dynamics, and establishes rDNA as the only known genomic target of nutritional insults found in mammalian and non-mammalian models.
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