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Design of synthetic yeast promoters via tuning of nucleosome architecture

Kathleen A. Curran, Nathan C. Crook, Ashty S. Karim, Akash Gupta, Allison M. Wagman and Hal S. Alper ()
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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

Nature Communications, 2014, vol. 5, issue 1, 1-8

Abstract: 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.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5002

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DOI: 10.1038/ncomms5002

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