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Design of synthetic yeast promoters via tuning of nucleosome architecture

Author

Listed:
  • Kathleen A. Curran

    (The University of Texas at Austin, 200 E Dean Keeton Street Stop C0400)

  • Nathan C. Crook

    (The University of Texas at Austin, 200 E Dean Keeton Street Stop C0400)

  • Ashty S. Karim

    (The University of Texas at Austin, 200 E Dean Keeton Street Stop C0400)

  • Akash Gupta

    (The University of Texas at Austin, 200 E Dean Keeton Street Stop C0400)

  • Allison M. Wagman

    (The University of Texas at Austin, 200 E Dean Keeton Street Stop C0400)

  • Hal S. Alper

    (The University of Texas at Austin, 200 E Dean Keeton Street Stop C0400
    Institute for Cellular and Molecular Biology, The University of Texas at Austin, 2500 Speedway Avenue)

Abstract

Model-based design of biological parts is a critical goal of synthetic biology, especially for eukaryotes. Here we demonstrate that nucleosome architecture can have a role in defining yeast promoter activity and utilize a computationally-guided approach that can enable both the redesign of endogenous promoter sequences and the de novo design of synthetic promoters. Initially, we use our approach to reprogram native promoters for increased expression and evaluate their performance in various genetic contexts. Increases in expression ranging from 1.5- to nearly 6-fold in a plasmid-based system and up to 16-fold in a genomic context were obtained. Next, we demonstrate that, in a single design cycle, it is possible to create functional, purely synthetic yeast promoters that achieve substantial expression levels (within the top sixth percentile among native yeast promoters). In doing so, this work establishes a unique DNA-level specification of promoter activity and demonstrates predictive design of synthetic parts.

Suggested Citation

  • Kathleen A. Curran & Nathan C. Crook & Ashty S. Karim & Akash Gupta & Allison M. Wagman & Hal S. Alper, 2014. "Design of synthetic yeast promoters via tuning of nucleosome architecture," Nature Communications, Nature, vol. 5(1), pages 1-8, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5002
    DOI: 10.1038/ncomms5002
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    Cited by:

    1. Ning Qin & Lingyun Li & Xiaozhen Wan & Xu Ji & Yu Chen & Chaokun Li & Ping Liu & Yijie Zhang & Weijie Yang & Junfeng Jiang & Jianye Xia & Shuobo Shi & Tianwei Tan & Jens Nielsen & Yun Chen & Zihe Liu, 2024. "Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Jan Zrimec & Xiaozhi Fu & Azam Sheikh Muhammad & Christos Skrekas & Vykintas Jauniskis & Nora K. Speicher & Christoph S. Börlin & Vilhelm Verendel & Morteza Haghir Chehreghani & Devdatt Dubhashi & Ver, 2022. "Controlling gene expression with deep generative design of regulatory DNA," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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