DNA Methylation Errors in Cloned Mouse Sperm by Germ Line Barrier Evasion
DNA Methylation Errors in Cloned Mouse Sperm by Germ Line Barrier Evasion
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DOI：
10.1095/biolreprod.116.138677
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发表时间：
2016-06-01
影响因子：
3.6
通讯作者：
Kono, Tomohiro
中科院分区：
文献类型：
--
作者：
Koike, Tasuku;Wakai, Takuya;Kono, Tomohiro
生殖系重编程屏障根据性别重置亲代表观遗传修饰，在受精时赋予哺乳动物胚胎全能性。然而，目前尚不清楚表观遗传错误是否在生殖系重编程过程中发生，然后传递给生殖细胞，从而传递给后代。为了确定克隆小鼠精子中的DNA甲基化错误，我们在本研究中使用目标亚硫酸氢盐后测序方法进行了全基因组DNA甲基化分析，解决了这个问题。两种体细胞克隆小鼠（CL1和CL7）精子基因组中差异甲基化的CpG位点数量显著增加（P = 0.0045和P = 0.0116）。结果，他们有更多的差异甲基化的CpG岛。然而，没有证据表明这些位点会传播到后代的精子基因组中。这些结果表明，由胚胎克隆引起的DNA甲基化错误通过避开生殖系重编程屏障传播到精子基因组。
The germ line reprogramming barrier resets parental epigenetic modifications according to sex, conferring totipotency to mammalian embryos upon fertilization. However, it is not known whether epigenetic errors are committed during germ line reprogramming that are then transmitted to germ cells, and consequently to offspring. We addressed this question in the present study by performing a genome-wide DNA methylation analysis using a target postbisulfite sequencing method in order to identify DNA methylation errors in cloned mouse sperm. The sperm genomes of two somatic cell-cloned mice (CL1 and CL7) contained significantly higher numbers of differentially methylated CpG sites (P = 0.0045 and P = 0.0116). As a result, they had higher numbers of differentially methylated CpG islands. However, there was no evidence that these sites were transmitted to the sperm genome of offspring. These results suggest that DNA methylation errors resulting from embryo cloning are transmitted to the sperm genome by evading the germ line reprogramming barrier.