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 whose role in meiosis was not previously clarified in detail, binds to both PRDM9 and pREC8, a phosphorylated meiosis-specific cohesin, in male meiotic cells.

We created a Ewsr1 conditional knockout mouse models to deplete EWSR1 before the onset of meiosis, and found that absence of EWSR1 causes meiotic arrest with decreased histone trimethylation at meiotic hotspots, impaired DNA double-strand break repair, and reduced crossover number. Our results demonstrate that EWSR1 is essential for promoting PRDM9-dependent histone methylation and normal meiotic progress, possibly by facilitating the linking between PRDM9-bound hotspots and the nascent chromosome axis through its component cohesin pREC8.

大多数哺乳动物的减数分裂重组需要通过组蛋白 3 赖氨酸 4 和赖氨酸 36 甲基转移酶 PRDM9 的作用激活重组热点，以确保双链断裂成功启动和修复。在这里，我们发现 EWSR1（一种在减数分裂中的作用之前尚未详细阐明的蛋白质）在雄性减数分裂细胞中与 PRDM9 和 pREC8（一种磷酸化减数分裂特异性粘连蛋白）结合。

我们创建了Ewsr1条件敲除小鼠模型，在减数分裂开始前耗尽 EWSR1，并发现 EWSR1 的缺失会导致减数分裂停滞，减数分裂热点处的组蛋白三甲基化减少，DNA 双链断裂修复受损，交叉次数减少。我们的结果表明，EWSR1 对于促进 PRDM9 依赖性组蛋白甲基化和正常减数分裂进程至关重要，可能是通过其成分粘连蛋白 pREC8 促进 PRDM9 结合热点与新生染色体轴之间的连接。