The epigenetic profile of germ cells, which is defined by modifications of DNA and chromatin, changes dynamically during their development. Many of the changes are associated with the acquisition of the capacity to support post-fertilization development. Our knowledge of this aspect has greatly increased- for example, insights into how the re-establishment of parental imprints is regulated. In addition, an emerging theme from recent studies is that epigenetic modifiers have key roles in germ-cell development itself--for example, epigenetics contributes to the gene-expression programme that is required for germ-cell development, regulation of meiosis and genomic integrity. Understanding epigenetic regulation in germ cells has implications for reproductive engineering technologies and human health.

Epigenetic modifications of histones regulate gene expression and chromatin structure. 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.

No abstract