Tachibana Makoto, Nozaki Masami, Takeda Naoki, Shinkai Yoichi
Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, Japan.
EMBO J. 2007 Jul 25;26(14):3346-59. doi: 10.1038/sj.emboj.7601767. Epub 2007 Jun 28.
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.
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关键表观遗传标记。G9a是常染色质中主要的哺乳动物H3K9甲基转移酶，对小鼠胚胎发育至关重要。在此我们描述G9a在生殖细胞发育中的作用。生殖系中G9a被特异性失活的突变小鼠由于成熟配子的急剧减少而表现出不育。G9a缺陷的生殖细胞在减数分裂前期表现出同步联会的紊乱。重要的是，G9a缺陷生殖细胞中H3K9的单甲基化和二甲基化（H3K9me1和2）显著减少，且G9a调控的基因在减数分裂期间过度表达，这表明G9a介导的表观遗传基因沉默对于减数分裂前期的正常进展至关重要。最后，我们表明H3K9me1和2在减数分裂前期受到动态且性别差异的调控。这一遗传和生化证据有力地表明，一组特定的H3K9甲基转移酶和去甲基酶协同调节配子发生。
