Target-site preferences of Sleeping Beauty transposons
Target-site preferences of Sleeping Beauty transposons
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DOI：
10.1016/j.jmb.2004.09.086
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发表时间：
2005-02-11
影响因子：
5.6
通讯作者：
Hackett, PB
中科院分区：
文献类型：
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作者：
Liu, GY;Geurts, AM;Hackett, PB
睡美人（Sleeping Beauty，SB）转座子是一种Tc 1/mariner家族转座子，可用于脊椎动物的基因转移、基因标签和人类基因治疗。在这项研究中，我们分析了SB转座子的靶位点偏好。在基因组水平，SB转座子相对于基因（外显子和内含子）和基因间区域的整合似乎相当随机，但不是在微观尺度上。尽管在靶位点附近似乎存在共有序列，但一级序列不是靶选择的决定因素。当在有限的地形上检查整合时，最常用于整合的位点与共有序列不匹配。相反，序列中固有的独特变形可以是用于目标选择的识别信号。变形的特征在于靶位点的角度，使得围绕插入位点的轴偏离中心，螺旋的旋转（扭转）是不均匀的，并且中心碱基对之间的距离增加。我们的观察提供了几个假设的见解转座过程。我们的观察结果表明，由V-步骤算法预测的双螺旋的特定变形可以区分TA位点，其在容纳SB转座子插入的偏好方面变化约16倍。(C)2004爱思唯尔有限公司保留所有权利。
The Sleeping Beauty (SB) transposon is a Tc1/mariner family transposon that has applications in vertebrate animals for gene transfer, gene-tagging, and human gene therapy. In this study, we analyzed the target-site preferences of the SB transposon. At the genomic level, integration of SB transposons with respect to genes (exons and introns) and intergenic regions appears fairly random but not on a micro-scale. Although there appears to be a consensus sequence around the vicinity of the target sites, the primary sequence is not the determining factor for target selection. When integrations were examined over a limited topography, the sites used most often for integration did not match the consensus sequence. Rather, a unique deformation inherent in the sequence may be a recognition signal for target selection. The deformation is characterized by an angling of the target site such that the axis around the insertion site is off-center, the rotation of the helix (twisting) is non-uniform and there is an increase in the distance between the central base-pairs. Our observations offer several hypothetical insights into the transposition process. Our observations suggest that particular deformations of the double helix predicted by the V-step algorithm can distinguish TA sites that vary by about 16-fold in their preferences for accommodating insertions of SB transposons. (C) 2004 Elsevier Ltd. All rights reserved.