of κB elements in 10 kb-promoter regions. p50 homodimer and NF-κB bind to virtually the same κB elements. Weight matrix for NF-κB in the JASPAR database [42] consists of sequences of the “NF-κB”-subtype that are also targets for the p50 homodimer (Figure 5A). p50 protein binds to κB sites as homodimer and therefore has slightly higher affinity for symmetric κB elements [51], [52]; this is reflected in the composition of the second κB matrix of the “p50 homodimer”-subtype present in the JASPAR database (Figure 5B). We used both matrices in the analysis (Figure 5). To increase prediction specificity we used a phylogenetic footprinting approach based on the observation that functional Transcription Factor Binding Sites (TFBS) are more often located in evolutionary conserved regions [53], [54]. Analysis of the 479 differentially expressed genes with phylogenetic footprinting of human-rat gene sequences demonstrated that 58 genes contain one or more putative κB binding sites for both p50 homodimer and NF-κB (the “NF-κB”-subtype), and 19 genes contain at least one putative “p50 homodimer”-subtype κB binding site (Table S4). Among 1164 control genes, 188 genes contain putative “NF-κB”-subtype whereas 77 genes putative “p50 homodimer”-subtype of κB binding sites.
