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.
Network biomarker for cell fate determination [Ravasi et al. Cell 2010]