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哺乳动物早期发育过程中的染色质和表观遗传修饰。

Chromatin and epigenetic modifications during early mammalian development.

机构信息

INRA, UMR 1198 Biologie du Développement et Reproduction, F-78350 Jouy en Josas, France.

出版信息

Anim Reprod Sci. 2012 Sep;134(1-2):45-55. doi: 10.1016/j.anireprosci.2012.08.010. Epub 2012 Aug 11.

DOI:10.1016/j.anireprosci.2012.08.010
PMID:22921722
Abstract

In mammals, the embryonic genome is transcriptionally inactive after fertilization and embryonic gene expression is initiated during the preimplantation developmental period, during so-called "embryonic genome activation (EGA)". EGA is dependent on the presence of the basal transcriptional machinery components but also on the parental genome reorganization after fertilization. Indeed, during the first cell cycles, the embryonic nuclei undergo intense remodelling that participates in the regulation of embryonic development. Among the mechanisms of this remodeling, it appears that modifications of epigenetic marks are essential especially at the time of embryonic genome activation. This review will focus on DNA methylation and histone modifications such as acetylation or methylation which are important to produce healthy embryos. We will also consider nuclear higher-order structures, such as chromosomes territories and pericentric heterochromatin clusters. The relevance of these chromatin epigenetic modifications has been sustained by the work performed on cloned embryos produced through nuclear transfer of somatic donor cells. It is indeed believed that incomplete reprogramming of the somatic nucleus, in other words, the incomplete re-establishment of the embryonic epigenetic patterns and peculiar nuclear organization may be among the causes of development failure of cloned animals. This will also be discussed in this review.

摘要

在哺乳动物中,胚胎基因组在受精后是转录不活跃的,胚胎基因表达是在着床前发育阶段开始的,这一过程被称为“胚胎基因组激活(EGA)”。EGA 依赖于基础转录机制成分的存在,也依赖于受精后亲本基因组的重排。事实上,在第一个细胞周期中,胚胎核经历了强烈的重塑,这参与了胚胎发育的调控。在这种重塑的机制中,表观遗传标记的修饰似乎是必不可少的,尤其是在胚胎基因组激活的时候。这篇综述将集中讨论 DNA 甲基化和组蛋白修饰,如乙酰化或甲基化,这些修饰对产生健康的胚胎很重要。我们还将考虑核的高级结构,如染色体区室和着丝粒异染色质簇。这些染色质表观遗传修饰的相关性已经通过核移植体细胞核产生的克隆胚胎的工作得到了证实。事实上,人们认为体细胞核的不完全重编程,换句话说,胚胎表观遗传模式和特殊核组织的不完全重建,可能是克隆动物发育失败的原因之一。这也将在本综述中进行讨论。

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