DNA transposons and retroviruses are important transgenic tools for genome engineering. An important consideration affecting the choice of transgenic vector is their insertion site preferences. Previous large-scale analyses of Ds transposon integration sites in plants were done on the basis of reporter gene expression or germline transmission, making it difficult to discern vertebrate integration preferences. Here, we compare over 1300 Ds transposon integration sites in zebrafish, with Tol2 transposon and retroviral integration sites. Genome-wide analysis shows that Ds integration sites in the presence or absence of marker selection are remarkably similar and distributed throughout the genome. No strict motif was found, but a preference for structural features in the target DNA associated with DNA flexibility (Twist, Tilt, Rise, Roll, Shift and Slide) was observed. Remarkably, this feature is also found in transposon and retroviral integrations in maize and mouse cells. Our findings show that structural features influence integration of heterologous DNA in genomes, and have implications for targeted genome engineering.\ud\ud
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机译:DNA转座子和逆转录病毒是用于基因组工程的重要转基因工具。影响转基因载体选择的重要考虑因素是它们的插入位点偏好。以前对植物中Ds转座子整合位点的大规模分析是根据报告基因表达或种系传递进行的,这使得难以辨别脊椎动物整合的偏好。在这里,我们比较了斑马鱼中1300多个Ds转座子整合位点,Tol2转座子和逆转录病毒整合位点。全基因组分析表明,在有或没有标记选择的情况下,Ds整合位点非常相似,并分布在整个基因组中。没有发现严格的基序,但是观察到对目标DNA中与DNA柔韧性有关的结构特征的偏好(扭曲,倾斜,上升,滚动,移位和滑动)。值得注意的是,在玉米和小鼠细胞的转座子和逆转录病毒整合中也发现了此功能。我们的发现表明,结构特征会影响异源DNA在基因组中的整合,并会对靶向基因组工程产生影响。\ ud \ ud
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