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• W2024459631 abstract "Comparison of Prdm9−/− and wild-type mice reveals a role for the PRDM9 protein in directing the recombination machinery away from important genomic regions. PRDM9, a histone H3 methyltransferase, is thought to determine the location of recombination hotspots through sequence-specific binding. By genome-wide mapping of hotspots in mice that carry different Prdm9 alleles, Galina Petukhova and colleagues conclude that PRDM9 determines the positions of almost all hotspots in the mouse genome, apart from those in the pseudo-autosomal region. A comparison of preferential locations of recombination initiation sites in the absence of PRDM9 and in wild-type mice reveals an unexpected role of the PRDM9 protein in sequestering the recombination machinery away from gene-promoter regions and other functional genomic elements. Genetic recombination occurs during meiosis, the key developmental programme of gametogenesis. Recombination in mammals has been recently linked to the activity of a histone H3 methyltransferase, PR domain containing 9 (PRDM9)1,2,3,4,5,6, the product of the only known speciation-associated gene in mammals7. PRDM9 is thought to determine the preferred recombination sites—recombination hotspots—through sequence-specific binding of its highly polymorphic multi-Zn-finger domain8. Nevertheless, Prdm9 knockout mice are proficient at initiating recombination9. Here we map and analyse the genome-wide distribution of recombination initiation sites in Prdm9 knockout mice and in two mouse strains with different Prdm9 alleles and their F1 hybrid. We show that PRDM9 determines the positions of practically all hotspots in the mouse genome, with the exception of the pseudo-autosomal region (PAR)—the only area of the genome that undergoes recombination in 100% of cells10. Surprisingly, hotspots are still observed in Prdm9 knockout mice, and as in wild type, these hotspots are found at H3 lysine 4 (H3K4) trimethylation marks. However, in the absence of PRDM9, most recombination is initiated at promoters and at other sites of PRDM9-independent H3K4 trimethylation. Such sites are rarely targeted in wild-type mice, indicating an unexpected role of the PRDM9 protein in sequestering the recombination machinery away from gene-promoter regions and other functional genomic elements." @default.
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• W2024459631 date "2012-05-01" @default.
• W2024459631 modified "2023-10-13" @default.
• W2024459631 title "Genetic recombination is directed away from functional genomic elements in mice" @default.
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• W2024459631 doi "https://doi.org/10.1038/nature11089" @default.
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