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真核转录激活因子增强原核基因表达的调控。

Enhanced regulation of prokaryotic gene expression by a eukaryotic transcriptional activator.

机构信息

Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA.

出版信息

Nat Commun. 2021 Jul 5;12(1):4109. doi: 10.1038/s41467-021-24434-9.

Abstract

Expanding the genetic toolbox for prokaryotic synthetic biology is a promising strategy for enhancing the dynamic range of gene expression and enabling new engineered applications for research and biomedicine. Here, we reverse the current trend of moving genetic parts from prokaryotes to eukaryotes and demonstrate that the activating eukaryotic transcription factor QF and its corresponding DNA-binding sequence can be moved to E. coli to introduce transcriptional activation, in addition to tight off states. We further demonstrate that the QF transcription factor can be used in genetic devices that respond to low input levels with robust and sustained output signals. Collectively, we show that eukaryotic gene regulator elements are functional in prokaryotes and establish a versatile and broadly applicable approach for constructing genetic circuits with complex functions. These genetic tools hold the potential to improve biotechnology applications for medical science and research.

摘要

拓展原核生物合成生物学的遗传工具包是增强基因表达动态范围和为研究和生物医药工程应用提供新的工程方法的一个很有前景的策略。在这里,我们扭转了将遗传元件从原核生物转移到真核生物的当前趋势,并证明激活真核转录因子 QF 及其相应的 DNA 结合序列可以转移到大肠杆菌中以引入转录激活,除了紧密的关闭状态。我们进一步证明,QF 转录因子可用于遗传器件中,这些器件以稳健和持续的输出信号响应低输入水平。总的来说,我们表明真核基因调控元件在原核生物中是有功能的,并建立了一种用于构建具有复杂功能的遗传电路的通用且广泛适用的方法。这些遗传工具有可能改进生物技术在医学科学和研究中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3679/8257575/3e3bbf10f0df/41467_2021_24434_Fig1_HTML.jpg

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