Missing the Mark: PRDM9-Dependent Methylation Is Required for Meiotic DSB Targeting

Abstract

PRDM9 determines the localization of meiotic recombination hotspots, which are associated with histone H3 methylation. It is not known whether PRDM9's methyltransferase activity is required or how some PRDM9 alleles can dominate the distribution of hotspots over other alleles. Diagouraga, Clément, and colleagues (2018) show that methyltransferase activity is required for hotspot localization and that this activity is additive in combination, suggesting that the dominance of particular alleles is simply proportional to the frequency of targeted sites.

Figure 1.. Meiotic DSB formation is proportional to PRDM9-dependent methylation

(A) PRDM9 proteins with different zinc finger arrays PRDM9^Cst (red) and PRDM9^Dom2 (blue) are expressed and bind different target sequences based upon their affinity. Once bound, PRDM9 methylates histone H3 (green circles). Meiotic DSBs (yellow stars) are equally likely to form at any methylated hotspot. (B) Similar to (A) except instead of wild-type PRDM9^Cst, a methylase-dead version is expressed: PRDM9^Cst-YF (red). Only PRDM9^Dom2 is capable of methylating its target hotspots. Meiotic DSBs are formed at similar levels to (A), except only at PRDM9^Dom2 hotspots.