同源重組是發(fā)生在雌雄配子減數(shù)分裂過(guò)程中的重要事件，在這一過(guò)程中,，來(lái)自父本和母本的同源染色體之間發(fā)生遺傳物質(zhì)的交換,，并穩(wěn)定遺傳給下一代。近期研究認(rèn)為,，哺乳動(dòng)物細(xì)胞的同源重組與一種叫做PRDM9（PR domain containing 9）的組蛋白H3甲基轉(zhuǎn)移酶的活性有關(guān),。研究人員認(rèn)為PRDM9能夠通過(guò)其高度重復(fù)的鋅指結(jié)構(gòu)域結(jié)合特定DNA序列，從而使結(jié)合該蛋白多的區(qū)域成為同源重組熱點(diǎn)區(qū)域,。本文中,，研究者發(fā)現(xiàn)敲除了PRDM9基因的小鼠仍然可以發(fā)生同源重組。
研究者對(duì)缺失了PRDM9基因的小鼠,、有不同prdm9等位基因的2個(gè)小鼠品系,，以及它們雜交的子代進(jìn)行了比較，發(fā)現(xiàn)PRDM9確實(shí)是決定除了假常染色體以為基因組所有區(qū)域重組熱點(diǎn)的關(guān)鍵基因,。令人驚訝的是,，PRDM9敲除的小鼠不但能夠進(jìn)行同源重組，而且與野生型小鼠相同,，在這些重組的熱點(diǎn)區(qū)域也能夠檢測(cè)到組蛋白H3K4甲基化的標(biāo)志,。但是，在缺失了PRDM9基因的小鼠細(xì)胞中,，同源重組大多發(fā)生在啟動(dòng)子區(qū),，以及一些不依賴PRDM9的H3K4甲基化區(qū)域。而這些區(qū)域在野生型小鼠的細(xì)胞中很少發(fā)生同源重組,。這一結(jié)果可能說(shuō)明,，PRDM9在同源重組中起到區(qū)分基因組中不同功能元件的作用。（生物谷 Bioon.com ）
doi:10.1038/nature11089
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Genetic recombination is directed away from functional genomic elements in mice
Kevin Brick, Fatima Smagulova, Pavel Khil, R. Daniel Camerini-Otero & Galina V. Petukhova
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.
