期刊
NATURE
卷 485, 期 7400, 页码 642-645出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature11089
关键词
-
资金
- NIDDK
- March of Dimes Foundation [5-FY07-667]
- NIH from NIGMS [1R01GM084104-01A1]
- USUHS [FS71HU, R071HU, CS71HU]
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.
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