Figure 4. Motif Analysis.

Motifs are accompanied by the occurrence frequency, N. Enriched motifs are highlighted in green, and depleted ones, in red. An occurrence frequency with a star means that the corresponding enrichment/depletion is statistically significant (P=1e-5). The motifs are sorted such that those at the ends have more significant p-values. (More details in Fig. S9h.)

(a) Systematic search of 3-TF motifs. The most enriched motif is the FFL. A particular example formed by STAT1, STAT3 and RUNX1 is highlighted. Here, the “+” sign on an edge indicates that the correlation between the gene expression of the source and the target across tissues is positive. Other motifs containing a toggle-switch regulation on top of the basic FFL design are also indicated.

(b) Proximal-Distal-PPI MIMs. Here we searched all motifs involving the co-regulation of two TFs (which could be either proximal or distal) with (or without) a protein-protein interaction between them. We found the motifs containing the protein-protein interaction tended to be enriched.

(c) miRNA-SIMs. This figure shows the 2 enriched motifs resulting from enumerating all motifs in which a miRNA targets two TFs that are connected in various ways. These 2 motifs contain a protein complex of 2 TFs and a cooperative pair of promoter and distal regulatory TFs.

(d) The auto-regulator motif is enriched in the TF-TF network: 28 of all TFs are auto-regulators. Moreover, auto-regulators are more likely to be repressors (-) relative to non-auto regulators, and they tend to have more ncRNAs as their targets.