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Nucleic Acids Research, 2001, Vol. 29, No. 3 774-782
© 2001 Oxford University Press

Phylogenetic footprinting of transcription factor binding sites in proteobacterial genomes

Lee Ann McCue1, William Thompson1, C. Steven Carmack1, Michael P. Ryan1, Jun S. Liu2, Victoria Derbyshire1 and Charles E. Lawrence1,3,*

1The Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany, NY 12201, USA, 2The Department of Statistics, Harvard University, Cambridge, MA 02138, USA and 3Computer Science Department, Rensselaer Polytechnic Institute, Troy, NY 12180, USA

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/.

* To whom correspondence should be addressed at: The Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany, NY 12201, USA. Tel: +1 518 402 5034; Fax: +1 518 473 2900; Email: lawrence{at}wadsworth.org


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