Functional dynamics of H3K9 methylation during meiotic prophase progression
Functional dynamics of H3K9 methylation during meiotic prophase progression
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DOI：
10.1038/sj.emboj.7601767
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发表时间：
2007-07-25
期刊：
影响因子：
11.4
通讯作者：
Shinkai, Yoichi
中科院分区：
文献类型：
--
作者：
Tachibana, Makoto;Nozaki, Masami;Shinkai, Yoichi
组蛋白H3赖氨酸9（H3K9）甲基化是异染色质形成和转录沉默的重要表观遗传标记。G9a是哺乳动物常染色质上主要的H3K9甲基转移酶，对小鼠胚胎发生至关重要。在这里，我们描述了G9a在生殖细胞发育中的作用。G9a在种系中特异性失活的突变小鼠由于成熟配子的急剧丧失而显示不育。G9a缺陷的生殖细胞在减数分裂前期表现出同步突触的扰动。重要的是，在G9a缺陷的生殖细胞中H3K9（H3K9me1和2）的单甲基化和二甲基化显著降低，并且在减数分裂期间G9a调节的基因过表达，这表明G9a介导的表观遗传基因沉默对于适当的减数分裂前期进展至关重要。最后，我们表明，H3K9me1和2的动态和性别差异调节减数分裂前期。这种遗传和生化证据强烈表明，一组特定的H3K9甲基转移酶和脱甲基酶协同调节配子发生。
Histone H3 lysine 9 (H3K9) methylation is a crucial epigenetic mark of heterochromatin formation and transcriptional silencing. G9a is a major mammalian H3K9 methyltransferase at euchromatin and is essential for mouse embryogenesis. Here we describe the roles of G9a in germ cell development. Mutant mice in which G9a is specifically inactivated in the germ-lineage displayed sterility due to a drastic loss of mature gametes. G9a-deficient germ cells exhibited perturbation of synchronous synapsis in meiotic prophase. Importantly, mono- and di-methylation of H3K9 (H3K9me1 and 2) in G9a-deficient germ cells were significantly reduced and G9a-regulated genes were overexpressed during meiosis, suggesting that G9a-mediated epigenetic gene silencing is crucial for proper meiotic prophase progression. Finally, we show that H3K9me1 and 2 are dynamically and sex-differentially regulated during the meiotic prophase. This genetic and biochemical evidence strongly suggests that a specific set of H3K9 methyltransferase(s) and demethylase(s) coordinately regulate gametogenesis.