PDF(Pubmed)
Abstract：
Sperm production and function require the correct establishment of DNA methylation patterns in the germline. Here, we examined the genome-wide DNA methylation changes during human spermatogenesis and its alterations in disturbed spermatogenesis. We found that spermatogenesis is associated with remodeling of the methylome, comprising a global decline in DNA methylation in primary spermatocytes followed by selective remethylation, resulting in a spermatids/sperm-specific methylome. Hypomethylated regions in spermatids/sperm were enriched in specific transcription factor binding sites for DMRT and SOX family members and spermatid-specific genes. Intriguingly, while SINEs displayed differential methylation throughout spermatogenesis, LINEs appeared to be protected from changes in DNA methylation. In disturbed spermatogenesis, germ cells exhibited considerable DNA methylation changes, which were significantly enriched at transposable elements and genes involved in spermatogenesis. We detected hypomethylation in SVA and L1HS in disturbed spermatogenesis, suggesting an association between the abnormal programming of these regions and failure of germ cells progressing beyond meiosis.
摘要：
精子的产生和功能需要在种系中正确建立DNA甲基化模式。这里,我们研究了人类精子发生过程中全基因组DNA甲基化的变化及其在精子发生紊乱中的变化。我们发现精子发生与甲基化的重塑有关，包括初级精母细胞DNA甲基化的全球下降，然后是选择性再甲基化，产生精子细胞/精子特异性甲基化组。精子细胞/精子中的低甲基化区域富含DMRT和SOX家族成员以及精子细胞特异性基因的特定转录因子结合位点。有趣的是，而SINE在整个精子发生过程中表现出差异甲基化，LINE似乎被保护免受DNA甲基化的变化。在受干扰的精子发生中，生殖细胞表现出相当大的DNA甲基化变化，在参与精子发生的转座因子和基因上显著富集。我们在受累的精子发生中检测到SVA和L1HS的低甲基化，提示这些区域的异常编程与生殖细胞减数分裂后的失败之间存在关联。
