Refined spatial temporal epigenomic profiling reveals intrinsic connection between PRDM9-mediated H3K4me3 and the fate of double-stranded breaks.
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IF: 46.297
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Cited by: 19
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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.

Keywords

Spatial Temporal Genomics
Spatial Temporal Epigenomics

MeSH terms

Animals
DNA Breaks, Double-Stranded
DNA Repair
Epigenesis, Genetic
Histone-Lysine N-Methyltransferase
Histones
Male
Meiotic Prophase I
Mice
Mice, Inbred C57BL
Mice, Knockout
Spermatogonia

Authors

Chen, Yao
Lyu, Ruitu
Rong, Bowen
Zheng, Yuxuan
Lin, Zhen
Dai, Ruofei
Zhang, Xi
Xie, Nannan
Wang, Siqing
Tang, Fuchou
Lan, Fei
Tong, Ming-Han

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