Genetic and Epigenetic Variation, but Not Diet, Shape the Sperm Methylome.
Genetic and Epigenetic Variation, but Not Diet, Shape the Sperm Methylome.
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DOI：
10.1016/j.devcel.2015.11.024
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发表时间：
2015-12-21
影响因子：
11.8
通讯作者：
Rando OJ
中科院分区：
文献类型：
--
作者：
Shea JM;Serra RW;Carone BR;Shulha HP;Kucukural A;Ziller MJ;Vallaster MP;Gu H;Tapper AR;Gardner PD;Meissner A;Garber M;Rando OJ
父亲的饮食可以影响后代的代谢表型，但这种代际信息传递的机制仍然不清楚。在这里，我们询问从食用三种饮食之一的小鼠获得的精子中的胞嘧啶甲基化模式，生成4个精子样本池和12个单独精子样本的全基因组甲基化图谱，以及61个基因组规模的甲基化图谱。我们发现，“表观变异”，无论是随机的或由于未知的人口或环境因素，是一个更强大的贡献者精子甲基化比饮食消费。胞嘧啶甲基化的变化是特别显着的串联重复家族，包括核糖体DNA（rDNA）重复，但rDNA甲基化与rDNA拷贝数的遗传变异密切相关，并不受父亲的饮食。这些结果确定了哺乳动物基因组中遗传和表观遗传不稳定性的位点，但反对精子胞嘧啶甲基化在后代代谢的饮食重编程中的直接作用。
Paternal diet can impact metabolic phenotypes in offspring, but mechanisms underlying such intergenerational information transfer remain obscure. Here, we interrogate cytosine methylation patterns in sperm obtained from mice consuming one of three diets, generating whole genome methylation maps for 4 pools of sperm samples and for 12 individual sperm samples, as well as 61 genome-scale methylation maps. We find that “epivariation”, either stochastic or due to unknown demographic or environmental factors, was a far stronger contributor to the sperm methylome than was the diet consumed. Variation in cytosine methylation was particularly dramatic over tandem repeat families, including ribosomal DNA (rDNA) repeats, but rDNA methylation was strongly correlated with genetic variation in rDNA copy number, and was not influenced by paternal diet. These results identify loci of genetic and epigenetic lability in the mammalian genome, but argue against a direct role for sperm cytosine methylation in dietary reprogramming of offspring metabolism.