RRC ID 88433
著者 Chen Y, Lyu R, Rong B, Zheng Y, Lin Z, Dai R, Zhang X, Xie N, Wang S, Tang F, Lan F, Tong MH.
タイトル Refined spatial temporal epigenomic profiling reveals intrinsic connection between PRDM9-mediated H3K4me3 and the fate of double-stranded breaks.
ジャーナル Cell Res
Abstract 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.
巻・号 30(3)
ページ 256-268
公開日 2020-3-1
DOI 10.1038/s41422-020-0281-1
PII 10.1038/s41422-020-0281-1
PMID 32047271
PMC PMC7054334
MeSH Animals DNA Breaks, Double-Stranded* DNA Repair* Epigenesis, Genetic Histone-Lysine N-Methyltransferase / metabolism* Histones / metabolism* Male Meiotic Prophase I Mice Mice, Inbred C57BL Mice, Knockout Spermatogonia* / cytology Spermatogonia* / metabolism
リソース情報
実験動物マウス RBRC05145