Dynamic alterations in the paternal epigenetic landscape following fertilization.
Dynamic alterations in the paternal epigenetic landscape following fertilization.
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DOI：
10.3389/fgene.2012.00143
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发表时间：
2012
影响因子：
3.7
通讯作者：
Carrell DT
中科院分区：
文献类型：
--
作者：
Jenkins TG;Carrell DT
胚胎发育是一个复杂且动态的过程，基因表达频繁变化，最终导致细胞分化和各种细胞系的定型。这些变化可能先于特定细胞中信号级联的变化和/或表观遗传程序的改变。表观遗传重塑过程在发育早期就开始了。事实上，精子和卵子结合后不久，父亲和母亲的表观遗传景观就会发生大规模的表观遗传变化。这些细胞的表观基因组包括 DNA 本身的修饰（以 DNA 甲基化的形式），以及核蛋白含量和修饰，例如组蛋白的修饰。精子染色质主要由鱼精蛋白包装，但受精后，精子原核发生重塑，其中母体来源的组蛋白取代鱼精蛋白，导致染色质松弛并最终父体原核解浓缩。此外，在第一次细胞分裂之前，主动 DNA 去甲基化发生在父本基因组中，有效地消除了许多精子发生衍生的甲基化标记。这种复杂的相互作用开始了两个单倍体细胞结合形成二倍体生物体的动态过程。这些事件的生物学对于理解有性生殖至关重要，但我们对所涉及机制的了解极其有限。本综述将探讨有关父本染色质受精后表观遗传改变的已知信息以及现有文献所暗示的含义。
Embryonic development is a complex and dynamic process with frequent changes in gene expression, ultimately leading to cellular differentiation and commitment of various cell lines. These changes are likely preceded by changes to signaling cascades and/or alterations to the epigenetic program in specific cells. The process of epigenetic remodeling begins early in development. In fact, soon after the union of sperm and egg massive epigenetic changes occur across the paternal and maternal epigenetic landscape. The epigenome of these cells includes modifications to the DNA itself, in the form of DNA methylation, as well as nuclear protein content and modification, such as modifications to histones. Sperm chromatin is predominantly packaged by protamines, but following fertilization the sperm pronucleus undergoes remodeling in which maternally derived histones replace protamines, resulting in the relaxation of chromatin and ultimately decondensation of the paternal pronucleus. In addition, active DNA demethylation occurs across the paternal genome prior to the first cell division, effectively erasing many spermatogenesis derived methylation marks. This complex interplay begins the dynamic process by which two haploid cells unite to form a diploid organism. The biology of these events is central to the understanding of sexual reproduction, yet our knowledge regarding the mechanisms involved is extremely limited. This review will explore what is known regarding the post-fertilization epigenetic alterations of the paternal chromatin and the implications suggested by the available literature.