title: The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli.
abstract: 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.
authors.affiliation: Department of Molecular Cell Biology and Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Mangan
authors.forename: S
authors.initials: S
authors.lastname: Itzkovitz
authors.forename: A
authors.initials: A
authors.lastname: Zaslaver
authors.forename: U
authors.initials: U
authors.lastname: Alon
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D005690:Galactose / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D006801:Humans; D007763:Lac Operon; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic; D014534:UDPglucose 4-Epimerase / Q000235:genetics / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D011993:Recombinant Fusion Proteins; D014534:UDPglucose 4-Epimerase; C020551:galactose epimerase; D005690:Galactose