[Design of artificial DNA binding proteins toward control and elucidation of cellular functions].
[Design of artificial DNA binding proteins toward control and elucidation of cellular functions].
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[用于控制和阐明细胞功能的人工 DNA 结合蛋白的设计]。
DOI：
10.1248/yakushi.12-00228
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
M. Imanishi
中科院分区：
文献类型：
--
作者：
M. Imanishi
人工转录因子可以在所需的时间调节特定基因的表达，对于化学生物学、细胞生物学和未来的基因治疗研究非常有用。C2 H2锌指基序是一种含锌蛋白质，被认为是最普遍的DNA结合基序。该基序对于设计具有所需DNA结合特异性的人工转录因子是有吸引力的，因为其特征性DNA结合性质：（1）每个基序识别3bp，（2）串联连接的模块结构，和（3）作为单体结合至非回文序列。利用这些性质，已经设计出具有新的DNA结合特性的人工DNA结合蛋白。通过改变两个3-锌指结构域之间的接头区域，人工6-锌指蛋白被开发出来，并显示出跳过DNA序列。通过改变锌配体之一来产生锌响应性转录因子。靶向核心时钟基因的人工锌指转录因子诱导细胞“昼夜节律”的相移。在此，我将总结上述人工锌指型DNA结合蛋白和转录因子的产生和功能。
An artificial transcription factor that can regulate the expression of specific genes at a desired time is very useful for research in chemical biology, cell biology, and future gene therapy. A C2H2 zinc finger motif, one of zinc-containing proteins, is known as the most ubiquitous DNA binding motif. The motif is attractive for designing artificial transcription factors with desired DNA binding specificities because of its characteristic DNA binding properties: (1) recognition of 3 bp per motif, (2) tandemly connected modular structure, and (3) binding to non-palindrome sequences as a monomer. Taking advantage of these properties, artificial DNA binding proteins with new DNA binding characteristics have been designed. By changing the linker region between two 3-zinc finger domains, artificial 6-zinc finger proteins were developed and shown to skip DNA sequences. Zinc-responsive transcription factors were created by altering one of the zinc ligands. An artificial zinc finger transcription factor targeting a core clock gene induced phase shifts of the cellular "circadian rhythm". Herein, I will summarize creation and function of the above-mentioned artificial zinc finger-type DNA binding proteins and transcription factors.