EWSR1 Regulates PRDM9-Dependent Histone 3 Methylation and Links Recombination Hotspots With the Chromosomal Axis
36 Pages Posted: 4 Apr 2018 Sneak Peek Status: Review CompleteMore...
Meiotic recombination in most mammals requires recombination hotspot activation through the action of the histone 3 lysine-4 and lysine-36 methyltransferase PRDM9 to ensure successful double-strand break initiation and repair. Here we show that EWSR1, a protein with a previously uncharacterized role in meiosis, binds to PRDM9 and increases the efficiency of trimethylation at hotspots in vivo. Additionally, EWSR1 links PRDM9-activated hotspots and the nascent chromosomal axis through the phosphorylated meiotic-specific cohesin REC8. Together, these two functions of EWSR1 direct the choice of which hotspots will be used for double-strand break formation and repair, assuring that a sufficient number of crossovers are properly positioned along the centromere-telomere axis. These results show that successful recombination and meiosis require proper association of activated hotspots with the chromosomal axis mediated by interactions between EWSR1, PRDM9, and pREC8.
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