Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
Animal Genomics and Improvement Laboratory, BARC, US Department of Agriculture, Agriculture Research Service, Beltsville, MD 20705, USA.
Gigascience. 2018 May 1;7(5). doi: 10.1093/gigascience/giy039.
Although sperm DNA methylation has been studied in humans and other species, its status in cattle is largely unknown.
Using whole-genome bisulfite sequencing (WGBS), we profiled the DNA methylome of cattle sperm through comparison with three somatic tissues (mammary gland, brain, and blood). Large differences between cattle sperm and somatic cells were observed in the methylation patterns of global CpGs, pericentromeric satellites, partially methylated domains (PMDs), hypomethylated regions (HMRs), and common repeats. As expected, we observed low methylation in the promoter regions and high methylation in the bodies of active genes. We detected selective hypomethylation of megabase domains of centromeric satellite clusters, which may be related to chromosome segregation during meiosis and their rapid transcriptional activation upon fertilization. We found more PMDs in sperm cells than in somatic cells and identified meiosis-related genes such asKIF2B and REPIN1, which are hypomethylated in sperm but hypermethylated in somatic cells. In addition to the common HMRs around gene promoters, which showed substantial differences between sperm and somatic cells, the sperm-specific HMRs also targeted to distinct spermatogenesis-related genes, including BOLL, MAEL, ASZ1, SYCP3, CTCFL, MND1, SPATA22, PLD6, DDX4, RBBP8, FKBP6, and SYCE1. Although common repeats were heavily methylated in both sperm and somatic cells, some young Bov-A2 repeats, which belong to the SINE family, were hypomethylated in sperm and could affect the promoter structures by introducing new regulatory elements.
Our study provides a comprehensive resource for bovine sperm epigenomic research and enables new discoveries about DNA methylation and its role in male fertility.
尽管人类和其他物种的精子 DNA 甲基化已得到研究，但牛的精子 DNA 甲基化状态在很大程度上仍是未知的。
通过与三种体组织（乳腺、脑和血液）进行比较，我们使用全基因组亚硫酸氢盐测序（WGBS）描绘了牛精子的 DNA 甲基化组。在全基因组 CpG、着丝粒卫星、部分甲基化域（PMD）、低甲基化区域（HMR）和常见重复序列的甲基化模式方面，牛精子与体细胞之间存在巨大差异。正如预期的那样，我们观察到启动子区域的低甲基化和活跃基因的体部的高甲基化。我们检测到中心粒卫星簇的大片段的选择去甲基化，这可能与减数分裂期间的染色体分离以及它们在受精后快速转录激活有关。我们发现精子细胞中的 PMD 比体细胞中多，并鉴定了减数分裂相关基因，如 KIF2B 和 REPIN1，它们在精子中低甲基化，但在体细胞中高甲基化。除了在精子和体细胞之间存在显著差异的常见基因启动子周围 HMR 外，精子特异性 HMR 还靶向到不同的精子发生相关基因，包括 BOLL、MAEL、ASZ1、SYCP3、CTCF、MND1、SPATA22、PLD6、DDX4、RBBP8、FKBP6 和 SYCE1。尽管常见重复序列在精子和体细胞中都高度甲基化，但一些属于 SINE 家族的年轻 Bov-A2 重复序列在精子中低甲基化，并且可以通过引入新的调控元件来影响启动子结构。
我们的研究为牛精子表观基因组学研究提供了全面的资源，并使我们能够对 DNA 甲基化及其在男性生育力中的作用有新的发现。
