PRDM9 methyltransferase is essential for meiotic DSB formation

The programmed formation of hundreds DNA double strand breaks (DSBs) is essential for proper meiosis and fertility. In mice and humans, the location of these breaks is determined by the meiosis-specific protein PRDM9, through the DNA binding specificity of its zinc finger domain. PRDM9 also has methyltransferase activity. Here, we show that this activity is required for H3K4me3 and H3K36me3 deposition and for DSB formation at PRDM9 binding sites. By analyzing mice that express two PRDM9 variants with distinct DNA binding specificities, we reveal severalthe basic principles of PRDM9-dependent DSB site determination, in which an excess of sites are designated through PRDM9 binding and subsequent histone methylation, from which a subset are selected for DSB formation. H3K4me3-, DMC1-ChIPseq experiments were performed on testis from different mouse lines