Discovering functional transcription factor binding from superimposed gene networks

The availability of entire genome sequences, coupled with genome-wide studies of gene expression, offers promise for discovering new pathways along with their regulatory programs. Clusters identified from gene co-expression networks (GCNs) reveal correlations between genes but say little about the mechanism behind their coregulation. We have constructed a co-binding network (CBN) to identify the potential combinations of transcription factors (TFs) that may regulate a set of genes. The CBN was built by connecting all pairs of genes bound by the same transcription factor observed in ChIP-Chip microarray experiments. We superimposed the CBN onto the GCN to identify clusters of genes in overlapping subnetworks. Applying our method to a GCN derived from four distantly related species, we identified transcription factor combinations for several conserved sub-networks in yeast.