Refined Spatial Temporal Epigenomic Profiling Reveals Intrinsic Connection Between PRDM9-mediated H3K4me3 and the Fate of Double-stranded Breaks

Overview

Journal Cell Res

Specialty Cell Biology

Date 2020 Feb 13

PMID 32047271

Citations 26

Authors

Yao Chen

Ruitu Lyu

Bowen Rong

Yuxuan Zheng

Zhen Lin

Ruofei Dai

Xi Zhang

Nannan Xie

Siqing Wang

Fuchou Tang

Fei Lan

Ming-Han Tong

Affiliations

Soon will be listed here.

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.

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