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Noise in transcription negative feedback loops: simulation and experimental analysis
Yann Dublanche1, Konstantinos Michalodimitrakis, Nico Kümmerer
1European Molecular Biology Laboratory (EMBL), Heildelberg, Germany.
Molecular Systems Biology
|August 3, 2006
Summary
Negative feedback loops reduce transcriptional noise, with optimal noise reduction occurring at a specific repression strength. This mechanism effectively suppresses both internal and external noise sources, like plasmid fluctuations.
Area of Science:
- Synthetic biology
- Gene regulatory networks
Background:
- Transcriptional noise can be controlled using negative feedback loops.
- Autoregulation via transcription factors (TFs) is a common biological motif.
Purpose of the Study:
- To investigate the impact of negative feedback loops on transcriptional noise.
- To analyze the noise characteristics of autoregulated genes and their downstream targets.
Main Methods:
- Construction and experimental analysis of three synthetic gene circuits.
- Mathematical modeling and simulation of gene regulatory network dynamics.
- Assessment of transcriptional noise and gene expression patterns.
Main Results:
- Self-repression significantly decreases transcriptional noise compared to unregulated promoters.
- Noise minimization by negative feedback exhibits a U-shaped behavior, optimal within a specific repression strength range.
- Strong repression by a self-repressed TF (sTF) on a downstream gene (DG) reduces DG noise and increases noise anti-correlation.
- Plasmid variation identified as a significant source of external noise, contributing to bimodal gene expression.
Conclusions:
- Negative feedback loops are crucial for suppressing transcriptional noise, both internal and external.
- Optimal noise control is achieved within a defined range of repression strength.
- Plasmid fluctuations are a key determinant of noise and bimodal expression in these synthetic circuits.