Genetic recombination is directed away from functional genomic elements in mice

Article

关键词: HISTONE H3 METHYLTRANSFERASE;    MEIOTIC RECOMBINATION;    PRDM9;    INITIATION;    HOTSPOTS;    SITES;    MOUSE;    IDENTIFICATION;    LANDSCAPE;    MEIOSIS;   

DOI  :  10.1038/nature11089

来源: SCIE

【 摘 要 】

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)(1-6), the product of the only known speciation-associated gene in mammals(7). PRDM9 is thought to determine the preferred recombination sites-recombination hotspots-through sequence-specific binding of its highly polymorphic multi-Zn-finger domain(8). Nevertheless, Prdm9 knockout mice are proficient at initiating recombination(9). 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 F-1 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 cells(10). 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.

【 授权许可】

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