Modular construction of mammalian gene circuits using TALE transcriptional repressors
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Author(s)
Li, Yinqing
Jiang, Yun
Chen, He
Liao, Weixi
Li, Zhihua
Weiss, Ron
Xie, Zhen
Date Issued
February 2015
Journal
Nature Chemical Biology
Publisher
Nature Publishing Group
Citation
Li, Yinqing, Yun Jiang, He Chen, Weixi Liao, Zhihua Li, Ron Weiss, and Zhen Xie. “Modular Construction of Mammalian Gene Circuits Using TALE Transcriptional Repressors.” Nat Chem Biol 11, no. 3 (February 2, 2015): 207–213.
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Author's final manuscript
Abstract
An important goal of synthetic biology is the rational design and predictable implementation of synthetic gene circuits using standardized and interchangeable parts. However, engineering of complex circuits in mammalian cells is currently limited by the availability of well-characterized and orthogonal transcriptional repressors. Here, we introduce a library of 26 reversible transcription activator–like effector repressors (TALERs) that bind newly designed hybrid promoters and exert transcriptional repression through steric hindrance of key transcriptional initiation elements. We demonstrate that using the input-output transfer curves of our TALERs enables accurate prediction of the behavior of modularly assembled TALER cascade and switch circuits. We also show that TALER switches using feedback regulation exhibit improved accuracy for microRNA-based HeLa cancer cell classification versus HEK293 cells. Our TALER library is a valuable toolkit for modular engineering of synthetic circuits, enabling programmable manipulation of mammalian cells and helping elucidate design principles of coupled transcriptional and microRNA-mediated post-transcriptional regulation.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/nchembio.1736
