Meiotic recombination is initiated by the formation of double-strand breaks (DSBs), which are repaired as either crossovers (COs) or noncrossovers (NCOs). In most mammals, PRDM9-mediated H3K4me3 controls the nonrandom distribution of DSBs; however, both the timing and mechanism of DSB fate control remain largely undetermined. Here, we generated comprehensive epigenomic profiles of synchronized mouse spermatogenic cells during meiotic prophase I, revealing spatiotemporal and functional relationships between epigenetic factors and meiotic recombination. We find that PRDM9-mediated H3K4me3 at DSB hotspots, coinciding with H3K27ac and H3K36me3, is intimately connected with the fate of the DSB. Our data suggest that the fate decision is likely made at the time of DSB formation: earlier formed DSBs occupy more open chromatins and are much more competent to proceed to a CO fate. Our work highlights an intrinsic connection between PRDM9-mediated H3K4me3 and the fate decision of DSBs, and provides new insight into the control of CO homeostasis.

中文翻译：

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完善的时空表观基因组学分析揭示了PRDM9介导的H3K4me3与双链断裂的命运之间的内在联系。

减数分裂重组是通过形成双链断裂（DSB）来启动的，双链断裂可通过交叉（CO）或非交叉（NCO）进行修复。在大多数哺乳动物中，PRDM9介导的H3K4me3控制着DSB的非随机分布。但是，DSB命运控制的时机和机制仍未确定。在这里，我们生成了减数分裂前期I期间同步小鼠生精细胞的综合表观基因组图谱，揭示了表观遗传因子与减数分裂重组之间的时空和功能关系。我们发现，在DSB热点，PRDM9介导的H3K4me3与H3K27ac和H3K36me3恰好相符，与DSB的命运息息相关。我们的数据表明，命运决定可能是在DSB成立时做出的：较早形成的DSB占据了更多的开放染色质，并且更有能力进行CO鉴定。我们的工作强调了PRDM9介导的H3K4me3与DSB命运决定之间的内在联系，并为控制CO稳态提供了新见解。