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着床前哺乳动物发育中的表观遗传学

Epigenetics in preimplantation mammalian development.

作者信息

Canovas Sebastian, Ross Pablo Juan

机构信息

LARCEL (Laboratorio Andaluz de Reprogramacion Celular), BIONAND, Centro Andaluz de Nanomedicina y Biotecnologia Campanillas, Malaga, Spain.

Department of Animal Science, University of California, Davis, California, USA.

出版信息

Theriogenology. 2016 Jul 1;86(1):69-79. doi: 10.1016/j.theriogenology.2016.04.020. Epub 2016 Apr 21.

Abstract

Fertilization is a very dynamic period of comprehensive chromatin remodeling, from which two specialized cells result in a totipotent zygote. The formation of a totipotent cell requires extensive epigenetic remodeling that, although independent of modifications in the DNA sequence, still entails a profound cell-fate change, supported by transcriptional profile modifications. As a result of finely tuned interactions between numerous mechanisms, the goal of fertilization is to form a full healthy new individual. To avoid the persistence of alterations in epigenetic marks, the epigenetic information contained in each gamete is reset during early embryogenesis. Covalent modification of DNA by methylation, as well as posttranslational modifications of histone proteins and noncoding RNAs, appears to be the main epigenetic mechanisms that control gene expression. These allow different cells in an organism to express different transcription profiles, despite each cell containing the same DNA sequence. In the context of replacement of spermatic protamine with histones from the oocyte, active cell division, and specification of different lineages, active and passive mechanisms of epigenetic remodeling have been revealed as critical for editing the epigenetic profile of the early embryo. Importantly, redundant factors and mechanisms are likely in place, and only a few have been reported as critical for fertilization or embryo survival by the use of knockout models. The aim of this review is to highlight the main mechanisms of epigenetic remodeling that ensue after fertilization in mammals.

摘要

受精是一个全面染色质重塑的非常动态的时期,两个特化细胞由此产生一个全能合子。全能细胞的形成需要广泛的表观遗传重塑,尽管这独立于DNA序列的修饰,但仍然需要深刻的细胞命运改变,并由转录谱修饰来支持。由于众多机制之间的精细调控相互作用,受精的目标是形成一个完整健康的新个体。为了避免表观遗传标记改变的持续存在,每个配子中包含的表观遗传信息在早期胚胎发育过程中会被重置。DNA通过甲基化的共价修饰,以及组蛋白和非编码RNA的翻译后修饰,似乎是控制基因表达的主要表观遗传机制。这些机制使得生物体中的不同细胞能够表达不同的转录谱,尽管每个细胞都包含相同的DNA序列。在精子鱼精蛋白被卵母细胞的组蛋白取代、活跃的细胞分裂以及不同谱系的特化背景下,表观遗传重塑的主动和被动机制已被揭示对编辑早期胚胎的表观遗传谱至关重要。重要的是,可能存在冗余的因子和机制,并且通过使用基因敲除模型,只有少数被报道对受精或胚胎存活至关重要。本综述的目的是突出哺乳动物受精后发生的表观遗传重塑的主要机制。

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