Efficient and Orthogonal Transcription Regulation by Chemically Inducible Artificial Transcription Factors.
Efficient and Orthogonal Transcription Regulation by Chemically Inducible Artificial Transcription Factors.
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DOI：
10.1021/acs.biochem.8b00741
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发表时间：
2018-10
期刊：
影响因子：
2.9
通讯作者：
W. Nomura;Daisuke Matsumoto;T. Sugii;Takuya Kobayakawa;H. Tamamura
中科院分区：
文献类型：
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作者：
W. Nomura;Daisuke Matsumoto;T. Sugii;Takuya Kobayakawa;H. Tamamura
基因组编辑工具的DNA结合特异性可用于基因调控。近年来，多种人工转录因子(ATF)被证明能够协同有效地调控基因表达。化学触发的蛋白质关联对于特定时间的功能调节是有用的。几个可诱导蛋白联合系统的组合可以使不同位点的多个基因以独立的时间进行调节。我们应用FKBP-雷帕霉素-FRB和GAI-赤霉素-GID系统进行基因调控，使用多个TALS和dCas9。结合现有系统，进行了报告基因分析；结果表明，在存在FRB或GAI效应结构域的情况下，基因表达分别受到雷帕霉素或赤霉素的调控。此外，内源基因的激活受到该系统的差异调控。这一成功表明，化学诱导的多个ATF可用于多基因的时间依赖调节，例如依赖于可编程表达时间和多基因差异表达的细胞现象的情况。
The DNA-binding specificity of genome editing tools can be applied to gene regulation. Recently, multiple artificial transcription factors (ATFs) were shown to synergistically and efficiently regulate gene expression. Chemically triggered protein associations are useful for functional regulation at specific timings. A combination of several inducible protein association systems could enable the regulation of multiple genes at different loci with independent timing. We applied the FKBP-rapamycin-FRB and GAI-gibberellin-GID systems for gene regulation using multiple TALEs and dCas9. By the combined use of currently available systems, reporter gene assays were performed; the results indicated that gene expression was regulated by rapamycin or gibberellin in the presence of the FRB or GAI effector domains, respectively. Furthermore, the activation of endogenous genes was differentially regulated by the system. This success suggests the usability of the chemically inducible multiple ATFs for the time-dependent regulation of multiple genes, such as the case for cellular phenomena that are dependent on the programmable timing of expression and the differential expression of multiple genes.