GSE112110
Genome wide map of DMC1 in testis of Stag3-/-, Rec8-/- and Stag3-/-Rec8-/- mice.
During mouse meiosis, DNA double-strand breaks (DSBs) are initiated by SPO11 at recombination hotspots (HSs), activated by PRDM9. Although activated HSs are marked by H3K4me3 and H3K36me3 histone modifications at open chromatin, most of the DSB-initiating and repair proteins are associated with the chromosome axis. This study addresses the mechanistic importance of the axis-associated cohesin proteins in DSB formation. We demonstrate that interactions between PRDM9 and the meiotic axis proteins STAG3 and REC8 are essential for efficient DSB formation. The absence of STAG3 or REC8 leads to inefficient meiotic DSB formation at HSs. STAG3 is critical for DSB formation, even at PRDM9-independent DSB-sites. Also, STAG3 and REC8 facilitate recruitment of the DSB-promoting proteins HORMAD1, IHO1 and MEI4 required for SPO11 activity. Together, these results support an evolutionarily conserved model in which axis-associated cohesin complexes recruit recombination-initiating proteins to DSB sites to promote meiotic recombination initiation. Overall design: Detection of meiotic double strand breaks sites in spermatocytes of Stag3-/-, Rec8-/- and Stag3-/-Rec8-/- mice and comparison with wild-type control This series includes the re-analysis of GSM1273023 from GSE52628. The methods and processed data files for this re-analyzed sample are available at the foot of this record.