Promoters Architecture-Based Mechanism for Noise-Induced Oscillations in a Single-Gene Circuit.

N Guisoni,L Diambra,D Monteoliva,Ramon Grima

doi:10.1371/journal.pone.0151086

N Guisoni, L Diambra + Show 2 more

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https://doi.org/10.1371/journal.pone.0151086

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Abstract

It is well known that single-gene circuits with negative feedback loop can lead to oscillatory gene expression when they operate with time delay. In order to generate these oscillations many processes can contribute to properly timing such delay. Here we show that the time delay coming from the transitions between internal states of the cis-regulatory system (CRS) can drive sustained oscillations in an auto-repressive single-gene circuit operating in a small volume like a cell. We found that the cooperative binding of repressor molecules is not mandatory for a oscillatory behavior if there are enough binding sites in the CRS. These oscillations depend on an adequate balance between the CRS kinetic, and the synthesis/degradation rates of repressor molecules. This finding suggest that the multi-site CRS architecture can play a key role for oscillatory behavior of gene expression. Finally, our results can also help to synthetic biologists on the design of the promoters architecture for new genetic oscillatory circuits.

Highlights

Oscillatory phenomena are an essential feature of biological systems and such behavior is present at different levels of the organization of the living matter
The results above show that the transitions between internal states of the cis-regulatory system (CRS) can constitute a mechanism for noise-induced oscillations in gene expression
Our stochastic analysis reveals that oscillations in the expression level of repressor are feasible in a broad range of parameters, while the corresponding macroscopic reaction rate equations predict the existence of stable fixed points

Summary

Introduction

Oscillatory phenomena are an essential feature of biological systems and such behavior is present at different levels of the organization of the living matter (cell, tissues, organs and individuals). The mechanism underlying such oscillations is a negative regulatory loop implemented in a gene-protein interaction network The complexity of such networks vary from highly complex ones, as those described for the cell division cycle, or the circadian rhythm, to the simplest ones which were synthetically implemented in prokaryotic cells [3, 4]. In this sense Stricker et al have shown that a synthetic single-gene circuit is able to display oscillatory behavior [5].

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