Fig. 2: Regulatory network hierarchies.
a TFs and b RBPs are systematically organized into a hierarchy, forming a joint TF-RBP regulatory network. Higher layer elements tend to regulate lower layer elements. c The regulatory potentials of TFs/RBPs to drive tumor-to-normal expression changes are shown as a heatmap; red and blue indicate up- and down-regulation respectively. d Elevated MYC regulatory activity is associated with reduced disease-specific survival (DSS) in breast cancer (i); MYC knockdown in MCF-7 leads to significantly larger expression reduction in MYC target genes (ii). e MYC expression is more positively correlated with its target genes as compared to other TFs (top); MYC frequently forms FFLs with NRF1. These are mostly coherent FFLs and OR-gate logic predominates (bottom). f Elevated SUB1 regulation activity is associated with reduced overall survival (OS) in lung cancer (i); SUB1 knockdown in HepG2 leads to reduced target gene expression (ii); Targets of SUB1 show slower mRNA decay rate (iii); for cancer-associated target genes of MYC and SUB1, gene expression is decreased with both MYC and SUB1 knockdown (KD), compared with knockdown of either MYC or SUB1 individually, and compared to control (iv).
