Structure and function of negative feedback loops at the interface of genetic and metabolic networks

TY - JOUR

T1 - Structure and function of negative feedback loops at the interface of genetic and metabolic networks

AU - Krishna, Sandeep

AU - Andersson, Anna M C

AU - Semsey, Szabolcs

AU - Sneppen, Kim

PY - 2006

Y1 - 2006

N2 - The molecular network in an organism consists of transcription/translation regulation, protein-protein interactions/modifications and a metabolic network, together forming a system that allows the cell to respond sensibly to the multiple signal molecules that exist in its environment. A key part of this overall system of molecular regulation is therefore the interface between the genetic and the metabolic network. A motif that occurs very often at this interface is a negative feedback loop used to regulate the level of the signal molecules. In this work we use mathematical models to investigate the steady state and dynamical behaviour of different negative feedback loops. We show, in particular, that feedback loops where the signal molecule does not cause the dissociation of the transcription factor from the DNA respond faster than loops where the molecule acts by sequestering transcription factors off the DNA. We use three examples, the bet, mer and lac systems in Escherichia coli, to illustrate the behaviour of such feedback loops.

AB - The molecular network in an organism consists of transcription/translation regulation, protein-protein interactions/modifications and a metabolic network, together forming a system that allows the cell to respond sensibly to the multiple signal molecules that exist in its environment. A key part of this overall system of molecular regulation is therefore the interface between the genetic and the metabolic network. A motif that occurs very often at this interface is a negative feedback loop used to regulate the level of the signal molecules. In this work we use mathematical models to investigate the steady state and dynamical behaviour of different negative feedback loops. We show, in particular, that feedback loops where the signal molecule does not cause the dissociation of the transcription factor from the DNA respond faster than loops where the molecule acts by sequestering transcription factors off the DNA. We use three examples, the bet, mer and lac systems in Escherichia coli, to illustrate the behaviour of such feedback loops.

KW - Down-Regulation

KW - Escherichia coli

KW - Gene Expression Regulation, Bacterial

KW - Models, Genetic

KW - Promoter Regions, Genetic

KW - Repressor Proteins

KW - Signal Transduction

KW - Transcription Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/nar/gkl140

DO - 10.1093/nar/gkl140

M3 - Journal article

C2 - 16684993

SN - 0305-1048

VL - 34

SP - 2455

EP - 2462

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 8

ER -