Artificial Transcription Factors Based on Multi‐Zinc Finger Motifs
Artificial Transcription Factors Based on Multi‐Zinc Finger Motifs
复制标题
基于多锌指基序的人工转录因子
DOI：
10.1002/chin.201022259
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发表时间：
2010
期刊：
影响因子：
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通讯作者：
Y. Sugiura
中科院分区：
文献类型：
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作者：
T. Morisaki;M. Imanishi;S. Futaki;Y. Sugiura
从调节生命科学研究和临床应用的生物学功能的角度来看，靶向任何所需基因的人工转录因子是非常有吸引力的。为了产生这样的转录因子，需要特异性DNA结合结构域来定位每个基因启动子的单个位点。C（2）H（2）型锌指基序具有识别三碱基DNA、以共价键串联重复、以单体形式工作等特点，是构建新型人工DNA结合蛋白的最佳框架之一。利用这些特征，迄今为止已经创建了针对各种DNA序列的多种锌指蛋白。为了应用于像人类基因组一样复杂的序列中的靶，必须要求DNA结合中的显著严格的特异性。缀合多个指（多锌指）使得能够识别足以寻址人类基因组中的单个位点的较长序列，而已知随着指基序的数量增加，通过体外实验与靶序列的平衡时间显著更长。我们最近的研究表明，多锌指型人工转录因子可以迅速激活报告基因。基因调控因子的研究引起了人们极大的兴趣，而基于多锌指结构的人工转录因子可能是一种优越的上级支架。
Artificial transcription factors targeting any desired genes are very attractive from the standpoint of regulating biological functions for life science studies and clinical applications. In order to generate such transcription factors, specific DNA binding domains are required to address a single site for each gene promoter. C (2) H (2) type zinc finger motif is one of the best frameworks to create new artificial DNA binding proteins for the following features: the zinc finger motif can recognize three bases DNA, be tandemly repeated by covalent linkage, and work as a monomer. Taking advantage of these features, manifold zinc finger proteins targeting various DNA sequences have been created so far. For application to a target in sequences as complex as the human genome, the significantly strict specificity in DNA binding must be required. Conjugating multiple fingers (multi-zinc fingers) enables to recognize longer sequences which are sufficient for addressing a single site in the human genome, whereas it has become known that as the number of finger motifs increases, the equilibrium time with the target sequence is significantly longer by in vitro experiments. Our recent study showed that the multi-zinc finger type artificial transcription factor could activate the reporter gene promptly. There is much interest in creating gene regulators, and the artificial transcription factors based on multi-zinc finger motifs could be a superior scaffold.