A histone H3 methyltransferase controls epigenetic events required for meiotic prophase (original) (raw)

Nature volume 438, pages 374–378 (2005)Cite this article

Abstract

Epigenetic modifications of histones regulate gene expression and chromatin structure1,2. Here we show that Meisetz (meiosis-induced factor containing a PR/SET domain and zinc-finger motif) is a histone methyltransferase that is important for the progression of early meiotic prophase. Meisetz transcripts are detected only in germ cells entering meiotic prophase in female fetal gonads and in postnatal testis. Notably, Meisetz has catalytic activity for trimethylation, but not mono- or dimethylation, of lysine 4 of histone H3, and a transactivation activity that depends on its methylation activity. Mice in which the Meisetz gene is disrupted show sterility in both sexes due to severe impairment of the double-stranded break repair pathway, deficient pairing of homologous chromosomes and impaired sex body formation. In _Meisetz_-deficient testis, trimethylation of lysine 4 of histone H3 is attenuated and meiotic gene transcription is altered. These findings indicate that meiosis-specific epigenetic events in mammals are crucial for proper meiotic progression.

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Acknowledgements

We thank N. Nakatsuji and S. Chuma for anti-SCP3 antibody; Y. Nishimune for TRA369 antibody; T. Noce for anti-mVASA antibody; H. Kai and Y. Seki for pcDNA3GAL4DBD; J. Miyazaki for pCAGGS; M. Saitou for confocal microscopy; and M. Tachibana and Y. Shinkai for GST-fused histone H3 expression vectors. This work was supported in part by CREST of JST (Japan Science and Technology Agency), and by grants-in-aid and Special Coordinating Funds for Promoting Science and Technology from the Ministry of Education, Science, Sports and Culture of Japan.

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  1. Katsuhiko Hayashi
    Present address: Wellcome Trust/Cancer Research UK, Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK

Authors and Affiliations

  1. Department of Molecular Embryology, Research Institute, Osaka Medical Center for Maternal and Child Health, Murodo-cho 840, 594-1101, Osaka, Izumi, Japan
    Katsuhiko Hayashi & Yasuhisa Matsui
  2. CREST, Japan Science and Technology Agency (JST), 332-0012, Saitama, Japan
    Katsuhiko Hayashi & Yasuhisa Matsui
  3. Department of Molecular Genetics, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, 545-8585, Osaka, Abeno-ku, Japan
    Kayo Yoshida
  4. Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, 980-8575, Sendai, Japan
    Yasuhisa Matsui

Authors

  1. Katsuhiko Hayashi
  2. Kayo Yoshida
  3. Yasuhisa Matsui

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Correspondence toYasuhisa Matsui.

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Hayashi, K., Yoshida, K. & Matsui, Y. A histone H3 methyltransferase controls epigenetic events required for meiotic prophase.Nature 438, 374–378 (2005). https://doi.org/10.1038/nature04112

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Editorial Summary

Managing meiosis

Meiosis is a unique cell division that is necessary for sexual reproduction; it produces functional haploid gametes and shuffles genomic information. Progression through meiosis is controlled by the proper orchestration of a number of meiotic genes. A candidate gene for regulating meiotic gene expression has now been identified. Meisetz, encoding a meiosis-specific histone H3 lysine 4-specific trimethyltransferase, is essential for meiotic recombination between homologous chromosomes in mice. Meisetz has essential functions in spermatocytes through epigenetic modification of chromatin, the first instance of a gene regulating epigenetic control of gene expression during meiotic progression.