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Engineering the Ultrasensitive Transcription Factors by Fusing a Modular Oligomerization Domain

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  • Junran Hou
  • Weiqian Zeng
  • Yeqing Zong
  • Zehua Chen
  • Chensi Miao
  • Baojun Wang
  • Chunbo Lou

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    Rights statement: © 2018 American Chemical Society

    Accepted author manuscript, 1.04 MB, PDF document

http://pubs.acs.org/doi/10.1021/acssynbio.7b00414
Original languageEnglish
Pages (from-to)1188–1194
Number of pages7
JournalACS Synthetic Biology
Volume7
Issue number5
Early online date7 May 2018
DOIs
Publication statusPublished - 18 May 2018

Abstract

The dimerization and high-order oligomerization of transcription factors has endowed them with cooperative regulatory capabilities that play important roles in many cellular functions. However, such advanced regulatory capabilities have not been fully exploited in synthetic biology and genetic engineering. Here, we engineered a C-terminally fused oligomerization domain to improve the cooperativity of transcription factors. First, we found that two of three designed oligomerization domains significantly increased the cooperativity and ultrasensitivity of a transcription factor for the regulated promoter. Then, seven additional transcription factors were used to assess the modularity of the oligomerization domains, and their ultrasensitivity was generally improved, as assessed by their Hill coefficients. Moreover, we also demonstrated that the allosteric capability of the ligand-responsive domain remained intact when fusing with the designed oligomerization domain. As an example application, we showed that the engineered ultrasensitive transcription factor could be used to significantly improve the performance of a “stripe-forming” gene circuit. We envision that the oligomerization modules engineered in this study could act as a powerful tool to rapidly tune the underlying response profiles of synthetic gene circuits and metabolic pathway controllers.

    Research areas

  • Hill coefficient, genetic circuit, high-order oligomerization domain, stripe-forming function, transcription factor, ultrasensitivity

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