PR-domain containing 9 (PRDM9) protein is a meiosis specific histone H3 lysine 4 (H3K4) methyltransferase, with a zinc finger domain at the C-terminus. Meiotic recombination hotspots in humans and mice are known to be sites for histone modification. PRDM9 has been shown to affect recombination profiles and meiotic recombination hotspot activity, by binding specific sequence motifs within or close to recombination hotspots (Baudat et al. 2010, Myers et al. 2010), and reorganizing chromatin structure. Variation within this protein has been proven to negatively affect human male fertility, with certain patients harboring variants at the PRDM9 locus exhibiting azoospermia. PRDM9 recognizes a specific sequence motif, but also acts at human hotspots lacking the motif, suggesting it is capable of acting in cis to regulate hotspot activity.
These specific sequence motifs also appear to be species specific, as the degenerate 13-bp motif associated with 40% of human hotspots does not function in chimpanzees, probably as a result of the rapidly evolving zinc finger domain (Myers et al. 2010). Subtle changes in the zinc finger array in humans can have global effects on recombination throughout the human genome, enhancing or decreasing the activity of a hotspot, or even creating entirely new hotspots (Berg et al. 2010). In addition to its role in regulating recombination hotspot activity, PRDM9 also appears to have a role in maintaining stability within the human genome, as variation in the PRDM9 gene can lead to large-scale genomic rearrangements and minisatellite instability in humans.