Dynamic changes of histone methylation in male germ cells during spermatogenesis

Spermatogenesis is a strictly regulated, complex process by which sperm cells are continuously produced throughout a person’s lifespan. This process includes 3 unique events: mitotic division, meiosis, and spermiogenesis. Many genes playing key roles in these events are mainly regulated by epigenetic mechanisms, especially DNA methylation and histone modifications. Histone methylation is one of the basic modifications in histones and contributes to the timely control of transcriptional activation and repression of the genes implicated in cell cycle progression, meiotic recombination, DNA repair, chromosome segregation, and chromatin condensation. For this purpose, specific histone methyltransferases perform methylation of the lysine and/or arginine residues of histones localized in nucleosomes. Added methyl groups can be removed by exclusive histone demethylases when necessary. Potential defects in correctly establishing histone methylation marks in H3K4, H3K9, H3K27, H3K36, H4R3, and H4K20 residues in male germline cells during spermatogenesis may result in the development of infertility. In this review, we comprehensively evaluate histone methylation dynamics in male germ cells, from spermatogonia to sperm cells. In addition, infertility development in males is discussed in terms of altered histone methylation accumulation because of altered expression of the histone methyltransferases and histone demethylases. Spermatogenesis is a strictly regulated, complex process by which sperm cells are continuously produced throughout a person’s lifespan. This process includes 3 unique events: mitotic division, meiosis, and spermiogenesis. Many genes playing key roles in these events are mainly regulated by epigenetic mechanisms, especially DNA methylation and histone modifications. Histone methylation is one of the basic modifications in histones and contributes to the timely control of transcriptional activation and repression of the genes implicated in cell cycle progression, meiotic recombination, DNA repair, chromosome segregation, and chromatin condensation. For this purpose, specific histone methyltransferases perform methylation of the lysine and/or arginine residues of histones localized in nucleosomes. Added methyl groups can be removed by exclusive histone demethylases when necessary. Potential defects in correctly establishing histone methylation marks in H3K4, H3K9, H3K27, H3K36, H4R3, and H4K20 residues in male germline cells during spermatogenesis may result in the development of infertility. In this review, we comprehensively evaluate histone methylation dynamics in male germ cells, from spermatogonia to sperm cells. In addition, infertility development in males is discussed in terms of altered histone methylation accumulation because of altered expression of the histone methyltransferases and histone demethylases.