Hundreds of motif pairs may facilitate enhancer-promoter interactions

Previous studies have shown that pairs of interacting transcription factors (TFs) bind to enhancers and promoters and contribute to their physical interactions. However, to date, we have limited knowledge about these interacting TF pairs. To identify such TF pairs, we systematically studied the co-occurrence of TF-binding motifs in interacting enhancer-promoter (EP) pairs in seven human cell lines. We discovered hundreds of motif pairs that significantly co-occur in enhancers and promoters of interacting EP pairs. We demonstrated that these motif pairs are biologically meaningful and significantly enriched with motif pairs of known interacting TF pairs. We also showed that the identified motif pairs facilitated the discovery of the interacting EP pairs. The predicted motifs and motif pairs are available at http://www.cs.ucf.edu/~xiaoman/ET/EPmotif/.