Open AccessNoise in transcription negative feedback loops: simulation and experimental analysis
Author(s) -
Dublanche Yann,
Michalodimitrakis Konstantinos,
Kümmerer Nico,
Foglierini Mathilde,
Serrano Luis
Publication year - 2006
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb4100081
Subject(s) - psychological repression , negative feedback , noise (video) , biology , positive feedback , bimodality , physics , transcription factor , transcription (linguistics) , gene expression , genetics , gene , computer science , quantum mechanics , engineering , voltage , artificial intelligence , galaxy , electrical engineering , image (mathematics) , linguistics , philosophy
Negative feedback loops have been invoked as a way to control and decrease transcriptional noise. Here, we have built three circuits to test the effect of negative feedback loops on transcriptional noise of an autoregulated gene encoding a transcription factor (TF) and a downstream gene (DG), regulated by this TF. Experimental analysis shows that self‐repression decreases noise compared to expression from a non‐regulated promoter. Interestingly enough, we find that noise minimization by negative feedback loop is optimal within a range of repression strength. Repression values outside this range result in noise increase producing a U‐shaped behaviour. This behaviour is the result of external noise probably arising from plasmid fluctuations as shown by simulation of the network. Regarding the target gene of a self‐repressed TF (sTF), we find a strong decrease of noise when repression by the sTF is strong and a higher degree of noise anti‐correlation between sTF and its target. Simulations of the circuits indicate that the main source of noise in these circuits could come from plasmid variation and therefore that negative feedback loops play an important role in suppressing both external and internal noise. An important observation is that DG expression without negative feedback exhibits bimodality at intermediate TF repression values. This bimodal behaviour seems to be the result of external noise as it can only be found in those simulations that include plasmid variation.