Hongyi Meng
Jianmin Zhang
Yang Liu
Qingjian Zou
Yi Gao
Huaqiang Yang
Liangxue Lai
aDepartment of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
bCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China
cSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, China
dCollege of Animal Science, South China Agricultural University, Guangzhou, 510642, China
More InformationCorresponding author: E-mail address: wyuchemzqj@126.com (Qingjian Zou);E-mail address: gaoyi6146@163.com (Yi Gao);E-mail address: yangh@scau.edu.cn (Huaqiang Yang);E-mail address: lai_liangxue@gibh.ac.cn (Liangxue Lai)
Publish Date:2020-11-25
Abstract
Abstract
Rapid, precise, and tunable regulation of protein abundance would be significantly useful in a variety of biotechnologies and biomedical applications. Here, we describe a system that allows tunable and rapid drug control of gene expression for either gene activation or inactivation in mammalian cells. We construct the system by coupling Tet-on 3G and small molecule-assisted shutoff systems, which can respectively induce transcriptional activation and protein degradation in the presence of corresponding small molecules. This dual-input drug inducer regulation system facilitates a bidirectional control of gene expression. The gene of interest can be precisely controlled by dual small molecules in a broad dynamic range of expression from overexpression to complete silence, allowing gene function study in a comprehensive expression profile. Our results reveal that the bidirectional control system enables sensitive dosage- and time-dependent regulation for either turn-on or shutoff of gene expression. We also apply this system for inducible genome editing and gene activation mediated by clustered regularly interspaced short palindromic repeats. The system provides an integrated platform for studying multiple biological processes by manipulating gene expression in a more flexible way.Keywords: Protein abundance,
Tet-on 3G,
SMASh,
Gene expression,
CRISPR,
Small molecule
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