Simultaneous Identification for Synergistic Transcription Factors and their Transcription Factor Binding Sites

Identifying transcription factor binding sites (TFBSs) is crucial for understanding the mechanism of transcriptional regulation. It is known that transcription factors (TFs) often cooperate to regulate genes. While traditional approaches can be used to discover binding motifs of a group of co-regulated genes, they often fail to accurately assign motifs to the corresponding TFs. Here, we consider two TFs together to infer their TFBSs and their synergistic relationship simultaneously. The basic idea is that if two TFs interact, their TFBSs, if distinct, would be conserved across species and coincided in the promoter regions of the genes they co-regulated. Applying our method to Saccharomyces cerevisiae chromatin immunoprecipitation data, we predicted 110 TF pairs with statistically significant motif assignments. A majority of these TF pairs have literature support to be synergistic, and the designated motifs to TFs match well with their known consensus. We further examined the synergism of predicted TF pairs in seven experimental conditions using ANOVA, and identified significant interactions.