DEtail-seq is an ultra-efficient and convenient method for meiotic DNA break profiling in multiple organisms

Programmed DNA double-strand break (DSB) formation is a crucial step in meiotic recombination, yet techniques for high-efficiency and precise mapping of the 3 ' ends of DSBs are still in their infancy. Here, we report a novel technique, named DNA End tailing and sequencing (DEtail-seq), which can directly and ultra-efficiently characterize the 3 ' ends of meiotic DSBs with near single-nucleotide resolution in a variety of species, including yeast, mouse, and human. We find that the 3 ' ends of meiotic DSBs are stable without significant resection in budding yeast. Meiotic DSBs are strongly enriched in de novo H3K4me3 peaks in the mouse genome at leptotene stage. We also profile meiotic DSBs in human and find DSB hotspots are enriched near the common fragile sites during human meiosis, especially at CCCTC-binding factor (CTCF)-associated enhancers. Therefore, DEtail-seq provides a powerful method to detect DSB ends in various species, and our results provide new insights into the distribution and regulation of meiotic DSB hotspots.

Automated summary

DNA End tailing and sequencing (DEtail-seq) is a novel technique that efficiently and accurately maps and studies the 3' ends of meiotic double-strand breaks (DSBs) in different species. The study found that the 3' ends of DSBs in budding yeast are stable and undergo minimal resection. In the mouse genome, DSBs at the 3' ends are strongly enriched in de novo H3K4me3 peaks during the leptotene stage. Meiotic DSB hotspots in humans are found to be enriched near common fragile sites, particularly at CCCTC-binding factor (CTCF)-associated enhancers. Therefore, DEtail-seq provides a powerful method for detecting DSB ends in various species and the findings offer new insights into the distribution and regulation of meiotic DSB hotspots.