We have combined and compared three methods for predicting functional interactions based on comparative genomics (methods based on conserved operons, protein fusions, and correlated evolution) and optimized these methods to predict coregulated sets of genes in 24 complete genomes, including S. cerevisiae, C. elegans, and 22 bacterial genomes. The method based on conserved operons was found to the most useful method for this purpose. Upstream regions of the genes making up these predicted regulons were used to search for regulatory motifs in 22 prokaryotic genomes using the motif-discovery program AlignACE. Many significant upstream motifs, including four known E. coli regulatory motifs, were found in this manner. The presence of a significant regulatory motif was used to refine the members of the predicted regulons in order to generate a final set of predicted regulons which share significant regulatory elements.
McGuire, and Church, G. M. Predicting regulons and their regulatory motifs by comparative genomics. (submitted to Nucleic Acids Research, June 2000).
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