Fig. 2: MESs predict endogenous β-catenin target gene expression.
From: Mutational scanning reveals oncogenic CTNNB1 mutations have diverse effects on signaling
a, Heatmap representation of MESs, showing the activity profile for every possible amino acid substitution at the CTNNB1 mutation hotspot, reconstructed from data shown in Fig. 1e. Individual scores are provided in Supplementary Table 2. The consensus motif for β-TRCP docking is shown in a beige rectangle above the heatmap, with known phosphorylation sites highlighted in red. b, Schematic to illustrate the derivation of clonal mouse ES cell lines genome-edited to express individual Ctnnb1 exon 3 mutations. Created in BioRender.com. c, Unsupervised clustering of Ctnnb-mutant clones based on global RNA-seq expression profiling shows co-clustering of clones with mutations of similar MES values (purple bar). d,e, Ten endogenous β-catenin target genes were selected based on the high correlation (>0.85) between transcript expression and dose of the GSK3β inhibitor CHIR99021 (d); transcript expression also correlated with MES values of the relevant exon 3 mutations (e). All r values and P values are from Pearson tests (two-sided); P values of <0.05 are highlighted in red.
