Design of synthetic yeast promoters via tuning of nucleosome architecture

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Model-based design of biological parts is a critical goal of synthetic biology, especially for eukaryotes. Here we demonstrate thatnucleosome 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 novodesign 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.

Original languageEnglish (US)
Article number4002
JournalNature communications
Volume5
DOIs
StatePublished - May 27 2014
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Design of synthetic yeast promoters via tuning of nucleosome architecture'. Together they form a unique fingerprint.

Cite this