1. Department of Molecular Embryology, Research Institute, Osaka Medical Center for Maternal and Child Health, Murodo-cho 840, Izumi, Osaka 594-1101, Japan
2. CREST, Japan Science and Technology Agency (JST), Saitama 332-0012, Japan
3. Department of Molecular Genetics, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
4. Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Sendai 980-8575, Japan
5. †Present address: Wellcome Trust/Cancer Research UK, Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK

Correspondence to: Yasuhisa Matsui^1,2,4 Correspondence and requests for materials should be addressed to Y.M. (Email: ymatsui@idac.tohoku.ac.jp).

Abstract

Epigenetic modifications of histones regulate gene expression and chromatin structure^{1, 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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