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| Status |
Public on Feb 12, 2020 |
| Title |
Refined spatial temporal epigenomic profiling reveals intrinsic connection between PRDM9-mediated H3K4me3 and the fate of double-stranded breaks |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
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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| Overall design |
We have applied chromatin ChIP-seq (Chromatin immunoprecipitation and sequencing) to spermatogenic cells for six critical histone modifications, including H3K4me3, H3K9me2, H3K9me3, H3K27me3, H3K36me3, and H3K27ac, and NOMe-seq (Nucleosome Occupancy and Methylome Sequencing) for the chromatin state, nucleosome positioning, and DNA methylation for each sample with two biological replicates. We also performed ChIP-seq and NOMe-seq for synchronous leptotene and zygotene from Prdm9-/-, Spo11-/-, and Dmc1-/- mice.
Examination of 6 different histone modifications in homogenous synchronous spermatogenic cells of 8 stages during meiotic process.
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| Contributor(s) |
Chen Y, Lyu R, Rong B, Zheng Y, Lin Z, Dai R, Zhang X, Xie N, Wang S, Tang F, Lan F, Tong M |
| Citation(s) |
32047271 |
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| Submission date |
Jun 10, 2019 |
| Last update date |
Apr 20, 2021 |
| Contact name |
Yuxuan Zheng |
| Organization name |
Fudan University
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| Street address |
825 Zhangheng Rd.
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| City |
Shanghai |
| ZIP/Postal code |
201203 |
| Country |
China |
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| Platforms (3) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL21273 |
HiSeq X Ten (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (186)
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| Relations |
| BioProject |
PRJNA548107 |
| SRA |
SRP200968 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE132446_RAW.tar |
62.5 Gb |
(http)(custom) |
TAR (of BED, BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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