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.