Nucleic Acids Research, 2000, Vol. 28, No. 22 4523-4530
© 2000 Oxford University Press
Predicting regulons and their cis-regulatory motifs by comparative genomics
Department of Genetics, Warren Alpert Building, Room 513, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
We have combined and compared three techniques 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 Saccharomyces cerevisiae, Caernorhabditis elegans and 22 prokaryotes. The method based on conserved operons was the most useful for this purpose. Upstream regions of the genes comprising these predicted regulons were then used to search for regulatory motifs in 22 prokaryotic genomes using the motif-discovery program AlignACE. Many significant upstream motifs, including five known Escherichia coli regulatory motifs, were identified in this manner. The presence of a significant regulatory motif was used to refine the members of the predicted regulons to generate a final set of predicted regulons that share significant regulatory elements.
* To whom correspondence should be addressed. Tel: +1 617 432 7562; Fax: +1 617 432 7266; Email: church{at}arep.med.harvard.edu
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