Conservation of methylation reprogramming in mammalian development: Aberrant reprogramming in cloned embryos
Conservation of methylation reprogramming in mammalian development: Aberrant reprogramming in cloned embryos
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DOI：
10.1073/pnas.241522698
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发表时间：
2001-11-20
影响因子：
11.1
通讯作者：
Reik, W
中科院分区：
文献类型：
--
作者：
Dean, W;Santos, F;Reik, W
小鼠胚胎在早期植入前发育中通过去甲基化进行全基因组甲基化重编程，随后进行再甲基化。在这里，我们表明，全基因组重编程是保守的几种哺乳动物物种，并询问它是否也发生在胚胎克隆使用高度甲基化的体细胞供体核。正常的牛、大鼠和猪的受精卵显示出一个去甲基化的父系基因组，表明主动去甲基化。在牛胚胎中，甲基化在卵裂过程中进一步降低，直到8细胞阶段，并且这种甲基化的降低之后是16细胞阶段的从头甲基化。在克隆的单细胞胚胎中，甲基化降低，这与主动去甲基化一致，但随后没有发生进一步的去甲基化。相反，在许多克隆胚胎中，类似于分化细胞的从头甲基化和甲基化模式的核重组过早发生。克隆，但不是正常的，桑椹胚有高度甲基化的核在所有的卵裂球，类似于那些成纤维细胞供体细胞。我们的研究表明，表观遗传重编程在大多数克隆胚胎中发生异常，不完全的重编程可能导致克隆效率低下。
Mouse embryos undergo genome-wide methylation reprogramming by demethylation in early preimplantation development, followed by remethylation thereafter. Here we show that genome-wide reprogramming is conserved in several mammalian species and ask whether it also occurs in embryos cloned with the use of highly methylated somatic donor nuclei. Normal bovine, rat, and pig zygotes showed a demethylated paternal genome, suggesting active demethylation. In bovine embryos methylation was further reduced during cleavage up to the eight-cell stage, and this reduction in methylation was followed by de novo methylation by the 16-cell stage. in cloned one-cell embryos there was a reduction in methylation consistent with active demethylation, but no further demethylation occurred subsequently. Instead, de novo methylation and nuclear reorganization of methylation patterns resembling those of differentiated cells occurred precociously in many cloned embryos. Cloned, but not normal, morulae had highly methylated nuclei in all blastomeres that resembled those of the fibroblast donor cells. Our study shows that epigenetic reprogramming occurs aberrantly in most cloned embryos; incomplete reprogramming may contribute to the low efficiency of cloning.