Uncovering cis regulatory codes using synthetic promoter shuffling

A. Kinkhabwala, C.C. Guet, PLoS One 3 (2008) e2030.

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Journal Article | Published | English
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Abstract
Revealing the spectrum of combinatorial regulation of transcription at individual promoters is essential for understanding the complex structure of biological networks. However, the computations represented by the integration of various molecular signals at complex promoters are difficult to decipher in the absence of simple cis regulatory codes. Here we synthetically shuffle the regulatory architecture-operator sequences binding activators and repressors-of a canonical bacterial promoter. The resulting library of complex promoters allows for rapid exploration of promoter encoded logic regulation. Among all possible logic functions, NOR and ANDN promoter encoded logics predominate. A simple transcriptional cis regulatory code determines both logics, establishing a straightforward map between promoter structure and logic phenotype. The regulatory code is determined solely by the type of transcriptional regulation combinations: two repressors generate a NOR: NOT (a OR b) whereas a repressor and an activator generate an ANDN: a AND NOT b. Three-input versions of both logics, having an additional repressor as an input, are also present in the library. The resulting complex promoters cover a wide dynamic range of transcriptional strengths. Synthetic promoter shuffling represents a fast and efficient method for exploring the spectrum of complex regulatory functions that can be encoded by complex promoters. From an engineering point of view, synthetic promoter shuffling enables the experimental testing of the functional properties of complex promoters that cannot necessarily be inferred ab initio from the known properties of the individual genetic components. Synthetic promoter shuffling may provide a useful experimental tool for studying naturally occurring promoter shuffling.
Publishing Year
Date Published
2008-04-30
Journal Title
PLoS One
Volume
3
Issue
4
Article Number
e2030
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Cite this

Kinkhabwala A, Guet CC. Uncovering cis regulatory codes using synthetic promoter shuffling. PLoS One. 2008;3(4):e2030. doi:10.1371/journal.pone.0002030
Kinkhabwala, A., & Guet, C. C. (2008). Uncovering cis regulatory codes using synthetic promoter shuffling. PLoS One, 3(4), e2030. https://doi.org/10.1371/journal.pone.0002030
Kinkhabwala, Ali, and Calin C Guet. “Uncovering Cis Regulatory Codes Using Synthetic Promoter Shuffling.” PLoS One 3, no. 4 (2008): e2030. https://doi.org/10.1371/journal.pone.0002030.
A. Kinkhabwala and C. C. Guet, “Uncovering cis regulatory codes using synthetic promoter shuffling,” PLoS One, vol. 3, no. 4, p. e2030, 2008.
Kinkhabwala A, Guet CC. 2008. Uncovering cis regulatory codes using synthetic promoter shuffling. PLoS One. 3(4), e2030.
Kinkhabwala, Ali, and Calin C. Guet. “Uncovering Cis Regulatory Codes Using Synthetic Promoter Shuffling.” PLoS One, vol. 3, no. 4, Public Library of Science, 2008, p. e2030, doi:10.1371/journal.pone.0002030.
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PMID: 18446205
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