Fig. 4

Analysis of conserved SDH-loss MRs. a Volcano plot showing SDHC-loss MEF transcriptomic signature. b SDHC-loss MEF MRs organized according to MR rank. c Venn diagram showing overlap of SDHC-loss MEF MRs and SDH-loss MRs inferred in PPGL human tumors. Green circle shows SDH-loss MRs inferred in the discovery cohort analysis. Red circle shows MRs inferred leveraging the validation cohort SDH-loss gene expression signature. Blue circle shows SDHC-loss iMEF MRs. Empiric p-value estimated by analysis of degree of overlap for iteratively-generated randomly-selected sets of TFs is shown. Putative conserved SDH-loss MRs are indicated. d Analysis of regulon log₂(fold-change) for putative conserved SDH-loss MRs. Regulon expression change for human SDH-loss PPGL tumors is shown on the x-axis. Regulon expression change for SDHC-loss MEFs is shown on the y-axis. Average size of mouse and human regulons are indicated by the size of data points. e Hierarchical clustering of MEF samples based upon ZFP423 regulon gene expression patterns (Exp: SDHC knockout iMEF line; Ctl: hemizygous control iMEF line). f Hierarchical clustering of MEF samples based upon SOX11 regulon gene expression patterns (Exp: SDHC knockout iMEF line; Ctl: hemizygous control iMEF line). g Analysis of synergy between ZFP423 and other mouse TFs. Regulon expression for ZFP423 is indicated as the leftmost column. Regulon expression for the various other TFs are indicated as the rightmost column. Regulon expression for the subset of co-regulated genes are shown in the middle column. h Analysis of synergy between SOX11 and other mouse TFs. Method of representation is the same as in panel (g)