The Incoherent Feed-forward Loop Accelerates the Response-time of the gal System of Escherichia coli

Complex gene regulation networks are made of simple recurring gene circuits called network motifs. One of the most common network motifs is the incoherent type-1 feed-forward loop (I1-FFL), in which a transcription activator activates a gene directly, and also activates a repressor of the gene. Math...

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Bibliographic Details
Published in:Journal of molecular biology 2006-03, Vol.356 (5), p.1073-1081
Main Authors: Mangan, S., Itzkovitz, S., Zaslaver, A., Alon, U.
Format: Article
Language:English
Subjects:
Animals
computational biology
design principles
Escherichia coli
Escherichia coli - genetics
Escherichia coli - metabolism
Escherichia coli Proteins - genetics
Escherichia coli Proteins - metabolism
Feedback, Physiological
fluorescent reporter
Galactose - metabolism
Gene Expression Regulation, Bacterial
Genes, Reporter
Humans
Lac Operon
network motifs
Promoter Regions, Genetic
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Signal Transduction - physiology
systems biology
Transcription, Genetic
UDPglucose 4-Epimerase - genetics
UDPglucose 4-Epimerase - metabolism
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Summary:Complex gene regulation networks are made of simple recurring gene circuits called network motifs. One of the most common network motifs is the incoherent type-1 feed-forward loop (I1-FFL), in which a transcription activator activates a gene directly, and also activates a repressor of the gene. Mathematical modeling suggested that the I1-FFL can show two dynamical features: a transient pulse of gene expression, and acceleration of the dynamics of the target gene. It is important to experimentally study the dynamics of this motif in living cells, to test whether it carries out these functions even when embedded within additional interactions in the cell. Here, we address this using a system with incoherent feed-forward loop connectivity, the galactose ( gal) system of Escherichia coli. We measured the dynamics of this system in response to inducing signals at high temporal resolution and accuracy by means of green fluorescent protein reporters. We show that the galactose system displays accelerated turn-on dynamics. The acceleration is abolished in strains and conditions that disrupt the I1-FFL. The I1-FFL motif in the gal system works as theoretically predicted despite being embedded in several additional feedback loops. Response acceleration may be performed by the incoherent feed-forward loop modules that are found in diverse systems from bacteria to humans.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2005.12.003