Combinatorial interactions among transcription factors (TFs) are critical for orchestrating gene expression programs during development. To identify these TF interaction complexes, we recently collaborated with the RIKEN Institute [link] to assemble a global atlas of combinatorial interactions among mammalian transcription factors [Ravasi et al. Cell 140(5):744-752 2010]. Two systems-wide data sets were generated in separate experiments in human and mouse: Physical protein-protein interaction among ~1200 TFs measured using the Mammalian Two Hybrid (M2H) system, and quantitative TF expression levels measured using qPCR across 34 adult tissues. This process identified ~800 high-stringency TF-TF interactions in each species, most of them novel. We have analyzed this network to identify transcription factor complexes as Network-Based biomarkers (see above) of tissue development. We are currently mining the combinatorial TF interaction network to identify additional transcription factor complexes that drive many other cell fate decisions decisions.
