PT  - JOURNAL ARTICLE
AU  - Mohamed Mahgoub
AU  - Jacob Paiano
AU  - Melania Bruno
AU  - Wei Wu
AU  - Sarath Pathuri
AU  - Xing Zhang
AU  - Sherry Ralls
AU  - Xiaodong Cheng
AU  - Andre Nussenzweig
AU  - Todd Macfarlan
TI  - Dual Histone Methyl Reader ZCWPW1 Facilitates Repair of Meiotic Double Strand Breaks
AID  - 10.1101/821603
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 821603
4099  - http://biorxiv.org/content/early/2019/10/29/821603.short
4100  - http://biorxiv.org/content/early/2019/10/29/821603.full
AB  - Meiotic crossovers result from homology-directed repair of double strand breaks (DSBs). Unlike yeast and plants, where DSBs are generated near gene promoters, in many vertebrates, DSBs are enriched at hotspots determined by the DNA binding activity of the rapidly evolving zinc finger array of PRDM9 (PR domain zinc finger protein 9). PRDM9 subsequently catalyzes tri-methylation of lysine 4 and lysine 36 of Histone H3 in nearby nucleosomes. Here, we identify the dual histone methylation reader ZCWPW1, which is tightly co-expressed during spermatogenesis with Prdm9 and co-evolved with Prdm9 in vertebrates, as an essential meiotic recombination factor required for efficient synapsis and repair of PRDM9-dependent DSBs. In sum, our results indicate that the evolution of a dual histone methylation writer/reader system in vertebrates facilitated a shift in genetic recombination away from a static pattern near genes towards a flexible pattern controlled by the rapidly evolving DNA binding activity of PRDM9.