Article
- The EMBO Journal (2007) 26, 3346 - 3359
- doi:10.1038/sj.emboj.7601767
Published online: 28 June 2007
Subject Category:
Functional dynamics of H3K9 methylation during meiotic prophase progression
Makoto Tachibana1, Masami Nozaki2, Naoki Takeda3 and Yoichi Shinkai1
- Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, Japan
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
- Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan
Correspondence to:
Makoto Tachibana, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. Tel.: +81 75 751 3991; Fax: +81 75 751-3991; E-mail: mtachiba@virus.kyoto-u.ac.jp
Yoichi Shinkai, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. Tel.: +81 75 751 3991; Fax: +81 75 751-3991; E-mail: yshinkai@virus.kyoto-u.ac.jp
Received 20 December 2006; Accepted 29 May 2007
Abstract
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.
Keywords:
- G9a,
- histone,
- meiotic prophase,
- methylation
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