Figure 2

Types of combinatorial regulation. Type 1 shows combinatorial regulation at the module level. The genes cdd, nupG, udp and deoC have two motifs in common (corresponding to the regulators CytR and CRP) and are co-expressed in condition set 1. This kind of control often seems to occur as a combination of a global regulator and a more specific one. Type 2 shows combinatorial regulation at the level of a connector gene. All genes of module 1 share two motifs, MarA and SoxS, and are co-expressed in a subset of conditions. For module 2 all genes are regulated by Fur. SodA, a connector gene, is shared by both modules and is thus regulated by the regulators of module 1 and module 2, but under a different set of conditions (as shown by the heatmap image), indicating that the corresponding regulators of both modules act independently of each other. Both types of interactions mentioned above can be identified by DISTILLER. Cases where condition-specific complex interactions between regulators result in such highly gene-specific expression patterns that genes are no longer found co-expressed in modules (type 3) cannot be detected by DISTILLER.