TopicPage for Predicted Regulons McCue 2002 of Escherichia coli K-12
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McCue and Lawrence have an Escherichia coli Transcription Factor Binding Sites webserver at The Wadsworth Center in New York. This site contains the results of their 2002 phylogenetic profiling study (McCue, 2002). In this study, they use a Bayesian Gibbs sampling algorithm to search for conserved DNA motifs upstream of 2086 E. coli genes. These genes had to have at least 50 bp of upstream intergenic DNA and have orthologs from closely related species for the phylogenetic profiling.
The EcoGene GenePages for these 2086 genes have links to the gene pages at Wadsworth that provide useful information on the orthologs and results of their study for each upstream region. They found 586 conserved DNA sites in front of the 2086 target genes that met their criteria for 586 significant motif predictions. They report that 485 of their motif predictions had not been previously determined to be TF binding sites, including new sites for known TFs and some novel predicted motifs probably corresponding to binding sites for novel TFs. The Escherichia coli Transcription Factor Binding Sites webserver describes how to interpret the information on the Wadsworth results gene pages linked to in the Resources menu of the EcoGene GenePages.
For genes in the latter half of the genome, the Wadsworth coordinates are the uncorrected U00096.1 coordinates and differ from the U00096.3 genome coordinates in EcoGene. Nonetheless, one can calculate the distance from the CDS to the TFBS for comparison with the RegulonDB TFBSs in EcoGene or convert to U00096.3 coordinates using the Interval Update EcoTool. The Wadsworth site references DBInteract as its source for previously reported TFBS regulatory sites. The GenePage links are in the Resources menu as "TF Binding Sites".
In addition to identifying putative TFBSs at orthologous positions, McCue et al. clustered the conserved orthologous motifs to identify putative regulons. Links are provided on 219 GenePages to a table of regulon predictions and those 219 GenePages are also linked to this TopicPage. In EcoGene 2.0 the PRedicted Regulon links are a special link at the bottom of the page but in EcoGene 3.0 the links are in the Resources menu are "Predicted Regulons". These 219 genes are in one or more of the 113 clusters in the Predicted E. coli regulons table at Wadsworth. A Wadsworth help page explains how to read the regulon table. The majority of the clusters, 66/113, are comprised of only one gene motif model, and thus do not appear to be actual clusters of sites comprising predicted regulons but rather are solo sites that have been excluded from the 47/113 clusters predicted to be regulons of 2 or more regulated monocistronic genes or operons.
The clusters have unique identifiers beginning with the letter "E" or "O", e.g. E582 for the PurR regulon motif. This cluster has 9 members, purM, purE, purR, purH, purL, cvpA, glyA, yicE and yjcD and the genome positions of the sites at the pur, glyA and cvpA genes correspond to known PurR TFBSs. yjcE and yjcD are thus predicted to be in the PurR regulon. The coordinates for the Wadsworth predictions can be accessed from the Resources menu and the coordinates for the known sites from RegulonDB are in the mouseover dialog of the TFBS icon in the TFBS pop-up window. You get the TFBS pop-up window when you click the brown TFBS arrows on the EcoMaps. (Hint, magnify the EcoMap with the icon to the right if the brown TFBS button doesn't bring up the TFBS pop-up boxes, which also have small intergenic repeats in the region shown). Likewise, other E clusters can be easily deduced as corresponding to known TFs, but this information is not explicitly listed at the Wadsworth. Some match-ups and comments will be collected here. We note the PurR regulon has many more members than predicted by the 9 in this cluster, with 26 members listed in RegulonDB.
Notes on the Regulon Predictions
YicE (COG2233) is a xanthine transporter and thus is reasonably regulated by PurR. YjcD (COG2252) is a known membrane protein that is predicted to be a xanthine/uracil permease. COG2233 and COG2252 are united in the NCBI's CD database Xan_ur_permease superfamily cl00967, indicating that YicE and YjcD are predicted to be distantly related homologs.
There is no mutant purR microarray data in EcoArray, but the response to organic solvent was interpreted as inducing the PurR regulon (Shimizu, 2005). EcoArray shows that they found yicE down-regulated 3-5 fold and yjcD down-regulated 2.6 fold, consistent with PurR regulation.
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