Fig. 4: Transcription factor activity in the gene body coordinates RNA and protein expression.

a Differential transcription factor footprints between tumor/met and normal. b Visualization of a FOSL2, a MAPK transcription factor, footprint within the MET gene body (top left). Comparison of genome-wide transcription factor footprints of FOSL2 between normal, tumor, and met (bottom left). Comparison of RNA expression of FOSL2 between normal, tumor, and met (top right). Comparison of protein expression of FOSL2 between normal, tumor, and met (bottom right). c Distance distribution of footprinted non-promoters linked to differential expression compared to distance between not active non-promoters to their gene target. Statistical test was two-sided Fisher’s exact test, comparing the number of gene body non-promoters (NP) vs distal NP (p = 1.3e−17). d Comparison of gene-wise correlation for genes with exonic vs intronic differential footprints. e Functional significance of activity based on gene sets. Left graph shows the top gene sets enriched in the differential protein subset of genes. The middle graph describes the top gene sets of footprinted differentially active genes. The left graph shows that footprinted differentially active genes that overlap with known thyroid cancer gene sets have expected changes in protein and gene accessibility between tumor/met vs normal. f Protein–protein interaction network of tissue-type-specific regulons.