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受精及胚胎植入前发育中的表观遗传学。

Epigenetics in fertilization and preimplantation embryo development.

机构信息

Division of Animal Sciences, University of Missouri, 164 ASRC 920 East Campus Drive, Columbia, MO 65211, USA.

出版信息

Prog Biophys Mol Biol. 2013 Dec;113(3):423-32. doi: 10.1016/j.pbiomolbio.2013.02.001. Epub 2013 Feb 27.

Abstract

Epigenetic reprogramming of the parental genomes upon fertilization is required for proper embryonic development. It has long been appreciated that asymmetric distribution of histone modifications as well as differences in the level of DNA methylation exist between the parental pronuclei in mammalian zygotes and during preimplantation development. The speed at which the paternal genome is demethylated after entering the oocyte and the fact that rapid demethylation occurs in the absence of DNA replication have led many to hypothesize that a DNA demethylase must exist. However, such an enzyme has not been found. That the genome of mammalian preimplantation embryos undergo a wave of global demethylation was first reported 25 years ago but only in the past three years has data surfaced that can partially explain the elusive nature of this phenomenon. In addition to the global reorganization of the methylation and histone modification patterns, oocyte development prior to germinal vesicle breakdown involves the production of numerous small RNA, including miRNA. Despite their presence, miRNA functional activity is thought to be limited in the mature mouse oocyte. Additionally, molecular signatures in the 3' untranslated region of maternally expressed transcripts may impact mRNA stability during the transcriptionally quiescent period following germinal vesicle breakdown and prior to the maternal to zygote transition. In this review, we reference some of the recent works which attempt to shed light into the importance of the dynamic epigenetic landscape observed during oocyte maturation and preimplantation embryo development in mammals.

摘要

受精时亲代基因组的表观遗传重编程对于胚胎的正常发育是必需的。长期以来,人们一直认为在哺乳动物受精卵和植入前胚胎发育过程中,亲代原核之间存在组蛋白修饰的不对称分布以及 DNA 甲基化水平的差异。父本基因组进入卵母细胞后被去甲基化的速度以及在没有 DNA 复制的情况下快速去甲基化的事实,使得许多人假设必须存在一种 DNA 去甲基酶。然而,这种酶尚未被发现。哺乳动物植入前胚胎的基因组经历了一波全基因组去甲基化,这一现象早在 25 年前就有报道,但直到最近三年,才出现了一些数据可以部分解释这种现象难以捉摸的本质。除了甲基化和组蛋白修饰模式的全局重组外,卵母细胞在生发泡破裂之前的发育过程中还会产生大量的小 RNA,包括 miRNA。尽管存在 miRNA,但在成熟的小鼠卵母细胞中,其功能活性被认为是有限的。此外,母源表达转录本 3'非翻译区中的分子特征可能会影响生发泡破裂后转录静止期和母源到合子过渡期的 mRNA 稳定性。在这篇综述中,我们参考了一些最近的研究工作,这些工作试图阐明在哺乳动物卵母细胞成熟和植入前胚胎发育过程中观察到的动态表观遗传景观的重要性。

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