Genome-wide methylation patterns in normal and uniparental early mouse embryos
Genome-wide methylation patterns in normal and uniparental early mouse embryos
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DOI：
10.1093/hmg/10.26.2983
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发表时间：
2001-12-15
影响因子：
3.5
通讯作者：
Haaf, T
中科院分区：
文献类型：
--
作者：
Barton, SC;Arney, KL;Haaf, T
在正常的二倍体小鼠胚胎中，随着受精卵进入第一个G1期，父亲基因组的主动去甲基化而不是母亲基因组的主动去甲基化仅在几个小时内发生，并且以高度协调的方式发生。这种合子去甲基化可能是精子基因组重编程以进行体细胞发育所必需的。免疫荧光染色的抗体对5-甲基胞嘧啶表明，受精卵的细胞机器不能去甲基化的第二个母亲的基因组在孤雌生殖，雌核发育和三倍体双雌胚胎或再甲基化的额外的（已经去甲基化）父亲的基因组在雄核发育和三倍体双雌胚胎。这表明，差异合子去甲基化的结果，在受精后，即精子核去凝聚和鱼精蛋白-组蛋白交换的父亲和母亲的染色质结构的重塑的差异。一部分来自正常交配的胚胎显示异常甲基化模式，其中一些与雄核发育或雌核发育胚胎中的甲基化模式无法区分。我们的结论是哺乳动物受精卵中的甲基化重编程缺陷导致早期妊娠失败的高发生率。
In the normal diploid mouse embryo, active demethylation of the paternal genome but not of the maternal genome occurs within only a few hours and in a highly coordinated fashion as the zygote proceeds through the first G1 phase. This zygotic demethylation may be necessary to reprogram the sperm genome for somatic development. Immunofluorescence staining with an antibody against 5-methylcytosine shows that the cellular machinery of the fertilized egg cannot demethylate the second maternal genome in parthenogenetic, gynogenetic and triploid digynic embryos or remethylate the additional (already demethylated) paternal genome in androgenetic and triploid diandric embryos. This suggests that differential zygotic demethylation results from differences in the remodeling of paternal and maternal chromatin structures after fertilization, i.e. sperm nuclear decondensation and protamine-histone exchange. A proportion of embryos derived from normal matings display abnormal methylation patterns some of which are indistinguishable from those in androgenetic or gynogenetic embryos. We conclude that methylation reprogramming defects in mammalian zygotes contribute to the high incidence of early pregnancy failure.