Refined spatial temporal epigenomic profiling reveals intrinsic connection between PRDM9-mediated H3K4me3 and the fate of double-stranded breaks  

作　　者：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 

机构地区：[1]State Key Laboratory of Molecular Biology,Shanghai Key Laboratory of Molecular Andrology,CAS Center for Excellence in Molecular Cell Science,Shanghai Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai 200031,China [2]Shanghai Key Laboratory of Medical Epigenetics,International Co-laboratory of Medical Epigenetics and Metabolism,Ministry of Science and Technology,Institutes of Biomedical Sciences,Fudan University,and Key Laboratory of Carcinogenesis and Cancer Invasion,Ministry of Education,Liver Cancer Institute,Zhongshan Hospital,Fudan University,Shanghai 200032,China [3]Beijing Advanced Innovation Center for Genomics,Biomedical Institute for Pioneering Investigation via Convergence,College of Life Sciences,Peking University,Beijing 100871,China [4]Ministry of Education Key Laboratory of Cell Proliferation and Differentiation,Beijing 100871,China [5]Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China

出　　处：《Cell Research》2020年第3期256-268,共13页细胞研究（英文版）

基　　金：supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19000000);the National Key R&D Program of China(2016YFC1000605 and 2018YFC1003401);the National Natural Science Foundation of China(31930034 and 31671553);the Science and Technology Commission of Shanghai Municipality(17JC1420102 and 19JC1415800);supported by the National Key R&D Program of China(2016YFA0101800 and 2018YFA0108700);the National Natural Science Foundation of China(31925010 and 91953121);Shanghai Municipal Science and Technology Major Project(2017SHZDZX01);supported by the National Natural Science Foundation of China(31625018);supported by the China Postdoctoral Science Foundation(2019M651607)。

摘　　要：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.

关 键 词：double CROSSOVER OCCUPY 

分 类 号：Q253[生物学—细胞生物学]