Maezawa So, Yukawa Masashi, Sakashita Akihiko, Barski Artem, Namekawa Satoshi H
Faculty of Science and Technology, Department of Applied Biological Science, Tokyo University of Science, Chiba 278-8510, Japan.
Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 45229, USA.
bioRxiv. 2025 Jan 11:2025.01.10.632457. doi: 10.1101/2025.01.10.632457.
DNA methylation patterns are inherited from the parental germline to the embryo. In mature sperm, the sites of unmethylated DNA are tightly coupled to sites of histone retention at gene regulatory elements that are implicated in paternal epigenetic inheritance. The timing and mechanism of site-specific DNA demethylation in the male germline currently remains unknown. Here, we perform genome-wide profiling of DNA methylation during spermatogenesis by capturing methylated DNA through interaction with a methyl-DNA binding protein domain (MBD). Our data demonstrate that there is a site-specific change in DNA methylation during the mitosis-to-meiosis transition. Importantly, the genomic sites that are demethylated during this transition predetermine nucleosome retention sites in spermatozoa. These results suggest that site-specific DNA demethylation during the mitosis-to-meiosis transition of spermatogenesis prepares embryonic gene expression after fertilization. We therefore propose DNA demethylation during spermatogenesis as a novel phase of epigenetic reprogramming that contributes to embryonic gene regulation.
DNA甲基化模式从亲代种系遗传至胚胎。在成熟精子中，未甲基化DNA位点与基因调控元件上组蛋白保留位点紧密相连，这些基因调控元件与父本表观遗传遗传有关。雄性生殖系中位点特异性DNA去甲基化的时间和机制目前尚不清楚。在此，我们通过与甲基-DNA结合蛋白结构域（MBD）相互作用捕获甲基化DNA，对精子发生过程中的DNA甲基化进行全基因组分析。我们的数据表明，在有丝分裂向减数分裂转变过程中，DNA甲基化存在位点特异性变化。重要的是，在此转变过程中发生去甲基化的基因组位点预先决定了精子中的核小体保留位点。这些结果表明，精子发生过程中有丝分裂向减数分裂转变期间的位点特异性DNA去甲基化为受精后的胚胎基因表达做好准备。因此，我们提出精子发生过程中的DNA去甲基化是表观遗传重编程的一个新阶段，有助于胚胎基因调控。
