Modeling DNA-binding of Escherichia coli sigma70 exhibits a characteristic energy landscape around strong promoters

Nucleic Acids Res. 2007;35(20):7003-10. doi: 10.1093/nar/gkm720. Epub 2007 Oct 16.

Abstract

We present a computational model of DNA-binding by sigma70 in Escherichia coli which allows us to extract the functional characteristics of the wider promoter environment. Our model is based on a measure for the binding energy of sigma70 to the DNA, which is derived from promoter strength data and used to build up a non-standard weight matrix. Opposed to conventional approaches, we apply the matrix to the environment of 3765 known promoters and consider the average matrix scores to extract the common features. In addition to the expected minimum of the average binding energy at the exact promoter site, we detect two minima shortly upstream and downstream of the promoter. These are likely to occur due to correlation between the two binding sites of sigma70. Moreover, we observe a characteristic energy landscape in the 500 bp surrounding the transcription start sites, which is more pronounced in groups of strong promoters than in groups of weak promoters. Our subsequent analysis suggests that the characteristic energy landscape is more likely an influence on target search by the RNA polymerase than a result of nucleotide biases in transcription factor binding sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • DNA-Directed RNA Polymerases / chemistry*
  • DNA-Directed RNA Polymerases / metabolism
  • Escherichia coli / chemistry*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Promoter Regions, Genetic*
  • Sigma Factor / chemistry*
  • Sigma Factor / metabolism
  • Transcription Initiation Site

Substances

  • Escherichia coli Proteins
  • Sigma Factor
  • RNA polymerase sigma 70
  • DNA-Directed RNA Polymerases