The histone modification reader ZCWPW1 links histone methylation to repair of PRDM9-induced meiotic double stand breaks

It is known that the histone modification writer PRDM9 deposits H3K4me3 and H3K36me3 marks at future DSB sites very early in meiosis, the nature of any proteins which can read such marks is unknown. Here, we demonstrate in vivo that ZCWPW1 is a H3K4me3 reader and show that its binding at chromatin promotes completion of DSB repair and synapsis in mouse testes. Based on multiple ChIP-seq and immunofluorescence analyses with mutants-including an H3K4me3-reader-dead variant of ZCWPW1 mice line-we establish that ZCWPW19s occupancy on chromatin is strongly but not exclusively promoted by the histone-modification activity of the PRDM9. ZCWPW1 localizes to DMC1-labelled DSB hotspots in a largely PRDM9-dependent manner, where it facilitates completion of synapsis by mediating the DSB repair process. In sum, our study demonstrates the function of a reader protein that carries out work resulting from an epigenetics-based recombination hotspot selection system in mammals.