Phylogenetic footprinting of transcription factor binding sites in proteobacterial genomes

• Published in: Nucleic acids research 2001-02, Vol.29 (3), p.774-782
• Main Authors: McCue, L, Thompson, W, Carmack, C, Ryan, M P, Liu, J S, Derbyshire, V, Lawrence, C E
• Format: Article
• Language: English
• Subjects: Base Sequence; Binding Sites - genetics; Databases, Factual; DNA, Bacterial - genetics; DNA, Bacterial - metabolism; Escherichia coli - genetics; Gammaproteobacteria - genetics; Genes, Bacterial - genetics; Genome, Bacterial; Phylogeny; Protein Binding; Sequence Alignment; Sequence Homology, Nucleic Acid; Transcription Factors - metabolism
• ISSN: 1362-4962; 0305-1048; 1362-4962
• DOI: 10.1093/nar/29.3.774

Toward the goal of identifying complete sets of transcription factor (TF)-binding sites in the genomes of several gamma proteobacteria, and hence describing their transcription regulatory networks, we present a phylogenetic footprinting method for identifying these sites. Probable transcription regulatory sites upstream of Escherichia coli genes were identified by cross-species comparison using an extended Gibbs sampling algorithm. Close examination of a study set of 184 genes with documented transcription regulatory sites revealed that when orthologous data were available from at least two other gamma proteobacterial species, 81% of our predictions corresponded with the documented sites, and 67% corresponded when data from only one other species were available. That the remaining predictions included bona fide TF-binding sites was proven by affinity purification of a putative transcription factor (YijC) bound to such a site upstream of the fabA gene. Predicted regulatory sites for 2097 E.coli genes are available at http://www.wadsworth.org/resnres/bioinfo/.