Jan 30, 2008

Co-regulation of metabolic genes is better explained by flux coupling than by network distance

PLoS Computational Biology
Richard A NotebaartBalázs Papp

Abstract

To what extent can modes of gene regulation be explained by systems-level properties of metabolic networks? Prior studies on co-regulation of metabolic genes have mainly focused on graph-theoretical features of metabolic networks and demonstrated a decreasing level of co-expression with increasing network distance, a naïve, but widely used, topological index. Others have suggested that static graph representations can poorly capture dynamic functional associations, e.g., in the form of dependence of metabolic fluxes across genes in the network. Here, we systematically tested the relative importance of metabolic flux coupling and network position on gene co-regulation, using a genome-scale metabolic model of Escherichia coli. After validating the computational method with empirical data on flux correlations, we confirm that genes coupled by their enzymatic fluxes not only show similar expression patterns, but also share transcriptional regulators and frequently reside in the same operon. In contrast, we demonstrate that network distance per se has relatively minor influence on gene co-regulation. Moreover, the type of flux coupling can explain refined properties of the regulatory network that are ignored by simple graph-theoreti...Continue Reading

  • References30
  • Citations56

Mentioned in this Paper

Metabolic Process, Cellular
Neuro-Oncological Ventral Antigen 2
In Silico
Gene Expression Regulation, Bacterial
Biochemical Pathway
Transcriptional Regulation
Alkalescens-Dispar Group
Genome
Enzymes, antithrombotic
Metabolic Networks

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