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表观遗传学在精子发生中的作用。

The role of epigenetics in spermatogenesis.

作者信息

Güneş Sezgin, Kulaç Tuba

机构信息

Department of Medical Biology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey.

出版信息

Turk J Urol. 2013 Sep;39(3):181-7. doi: 10.5152/tud.2013.037.

Abstract

Male germ cells have a unique morphology and function to facilitate fertilization. Sperm deoxyribonucleic acid (DNA) is highly condensed to protect the paternal genome during transfer from male to oocyte. Sperm cells undergo extensive epigenetic modifications during differentiation to become a mature spermatozoon. Epigenetic modifications, including DNA methylation, histone modifications, and chromatin remodeling are substantial regulators of spermatogenesis. DNA hypermethylation is associated with gene silencing. Meanwhile, hypomethylation is associated with gene expression. In sperm cells, promoters of developmental genes are highly hypomethylated. Proper DNA methylation is essential for embryo development. Histone modifications are chemical modifications that change the DNA-binding capacity of histones and the accessibility of regulatory factors to the DNA, thereby altering gene expression. Phosphorylation, methylation, acetylation, and ubiquitination are primary modifications of lysine and serine residues on histone tails. In addition to somatic histones, testis-specific histone variants are expressed, including histone H2B in mature sperm. The replacement of histones with protamines is a crucial step in spermatogenesis. Histone hyper-acetylation induces a loose chromatin structure and facilitates topoisomerase-induced DNA strand breaks. As a result, histones are replaced with transition proteins. Next, the transition proteins are replaced with protamines that induce compaction of sperm DNA. This review provides an overview of epigenetic changes during spermatogenesis.

摘要

雄性生殖细胞具有独特的形态和功能以促进受精。精子脱氧核糖核酸(DNA)高度浓缩,以便在从雄性向卵母细胞转移过程中保护父本基因组。精子细胞在分化为成熟精子的过程中会经历广泛的表观遗传修饰。表观遗传修饰,包括DNA甲基化、组蛋白修饰和染色质重塑,是精子发生的重要调节因子。DNA高甲基化与基因沉默相关。同时,低甲基化与基因表达相关。在精子细胞中,发育基因的启动子高度低甲基化。适当的DNA甲基化对胚胎发育至关重要。组蛋白修饰是化学修饰,可改变组蛋白与DNA的结合能力以及调节因子对DNA的可及性,从而改变基因表达。磷酸化、甲基化、乙酰化和泛素化是组蛋白尾部赖氨酸和丝氨酸残基的主要修饰。除了体细胞组蛋白外,还表达睾丸特异性组蛋白变体,包括成熟精子中的组蛋白H2B。用鱼精蛋白取代组蛋白是精子发生中的关键步骤。组蛋白高度乙酰化会诱导染色质结构松散,并促进拓扑异构酶诱导的DNA链断裂。结果,组蛋白被过渡蛋白取代。接下来,过渡蛋白被鱼精蛋白取代,鱼精蛋白会诱导精子DNA的压缩。本综述概述了精子发生过程中的表观遗传变化。

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