Dynamics of sequestration-based gene regulatory cascades

Nucleic Acids Research
Tatenda ShoperaTae Seok Moon

Abstract

Gene regulatory cascades are ubiquitous in biology. Because regulatory cascades are integrated within complex networks, their quantitative analysis is challenging in native systems. Synthetic biologists have gained quantitative insights into the properties of regulatory cascades by building simple circuits, but sequestration-based regulatory cascades remain relatively unexplored. Particularly, it remains unclear how the cascade components collectively control the output dynamics. Here, we report the construction and quantitative analysis of the longest sequestration-based cascade in Escherichia coli. This cascade consists of four Pseudomonas aeruginosa protein regulators (ExsADCE) that sequester their partner. Our computational analysis showed that the output dynamics are controlled in a complex way by the concentration of the unbounded transcriptional activator ExsA. By systematically varying the cascade length and the synthesis rate of each regulator, we experimentally verified the computational prediction that ExsC plays a role in rapid circuit responses by sequestering the anti-activator ExsD, while ExsD increases response times by decreasing the free ExsA concentration. In contrast, when additional ExsD was introduced to t...Continue Reading

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Citations

Dec 13, 2018·Nucleic Acids Research·Xuedong ZhengXiaopeng Wei
Jul 10, 2018·Nucleic Acids Research·Daniela PintoGeorg Fritz

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Methods Mentioned

BETA
PCR

Software Mentioned

ExsADCE
ExsAD
MATLAB
FlowJo

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