Distinct H3K9me3 and DNA methylation modifications during mouse spermatogenesis
Distinct H3K9me3 and DNA methylation modifications during mouse spermatogenesis
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小鼠精子发生过程中独特的 H3K9me3 和 DNA 甲基化修饰
DOI：
10.1074/jbc.ra119.010496
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发表时间：
2019-12-06
影响因子：
4.8
通讯作者：
Liu, Wenqiang
中科院分区：
文献类型：
--
作者：
Liu, Yingdong;Zhang, Yanping;Liu, Wenqiang
DNA甲基化和组蛋白修饰在精子发生过程中对许多基因和重复区域的表达起着关键的调节作用。然而，雄性生殖细胞中这些过程的分子细节仍有待解决。在这里，我们使用分离的小鼠精子细胞，超低输入天然芯片序列(ULI-NChIP-Seq)和全基因组亚硫酸盐测序(WGBS)，研究了小鼠精子发生过程中全基因组DNA甲基化模式和组蛋白3-赖氨酸-9三甲基化(H3K9me3)修饰。我们发现DNA甲基化和H3K9me3在精子发生过程中的启动子和重复元件上具有不同的序列偏好和动态。组蛋白基因启动子上的H3K9me3修饰在圆形精子细胞中高度丰富。H3K9me3对长末端重复序列(LTRs)和长散布核元件(LINE)的修饰参与了沉默这些区域的活跃转录，并重建了DNA甲基化。此外，X染色体上的H3K9me3重塑与减数分裂性染色体失活和精子细胞性染色体的部分转录再激活有关。我们的发现还揭示了精子发生过程中父亲和母亲生殖系印记控制区(GICR)的DNA甲基化模式和H3K9me3修饰谱。综上所述，我们的结果提供了小鼠精子发生过程中H3K9me3修饰的全基因组图谱，这可能有助于理解男性生殖障碍。
DNA methylation and histone modifications critically regulate the expression of many genes and repeat regions during spermatogenesis. However, the molecular details of these processes in male germ cells remain to be addressed. Here, using isolated murine sperm cells, ultra-low?input native ChIP-Seq (ULI-NChIP-Seq), and whole genome bisulfite sequencing (WGBS), we investigated genome-wide DNA methylation patterns and histone 3 Lys-9 trimethylation (H3K9me3) modifications during mouse spermatogenesis. We found that DNA methylation and H3K9me3 have distinct sequence preferences and dynamics in promoters and repeat elements during spermatogenesis. H3K9me3 modifications in histones at gene promoters were highly enriched in round spermatids. H3K9me3 modification on long terminal repeats (LTRs) and long interspersed nuclear elements (LINEs) was involved in silencing active transcription from these regions in conjunction with reestablishment of DNA methylation. Furthermore, H3K9me3 remodeling on the X chromosome was involved in meiotic sex chromosome inactivation and in partial transcriptional reactivation of sex chromosomes in spermatids. Our findings also revealed the DNA methylation patterns and H3K9me3 modification profiles of paternal and maternal germline imprinting control regions (gICRs) during spermatogenesis. Taken together, our results provide a genome-wide map of H3K9me3 modifications during mouse spermatogenesis that may be helpful for understanding male reproductive disorders.