Fig. 6: CADM1 variants affect genes associated with the ‘biological rhythms’ process.
a, Heatmap of differentially expressed genes in CADM1-mutant cells. Heatmap of differentially expressed genes in H295R cells transduced with EV, WT (442- and 453-amino acid isoforms), mutant CADM1 (V380D and G379D in both isoforms) or untransduced (UT). The columns represent different conditions (in triplicates) in the transduction experiments as labeled in b. Each row represents a gene whose mean expression was either upregulated >1.5-fold or downregulated <0.7-fold in variant transduced cells, compared to WT (two-sided one-way ANOVA P < 0.001). Centroid clustering was performed using cluster 3. Yellow represents upregulation and blue represents downregulation of genes as specified by color bar in b. The full heatmap is provided as Source Data Fig. 6. b, Zoomed image of heatmap in a displaying top 36 genes and clusters including genes associated with ‘biological rhythms’ process and GJA1. The top 36 genes were differentially regulated whether unstimulated (left half of heatmap) or stimulated by Ang II (right half, 10 nM for 24 h). However, for genes associated with ‘biological rhythms’ (highlight by bracket with arrow), the differential regulation was more apparent when the transduced cells were stimulated by Ang II. To note, transduction of H295R cells with both G379D and V380D mutant CADM1 substantially increased GJA1 mRNA expression in both isoforms. Genes of interest that are mentioned in the main text are arrowed. c, Genes associated with ‘biological rhythms’ process were differentially regulated in CADM1-mutant cells. RNA-seq of mutant CADM1-transduced cells reveals the most upregulated process associated with the 425 differentially expressed genes was ‘biological rhythms’. Clock genes associated with E-box factors and RORE target genes are highlighted by brackets. Graph shows the fold change of mRNA expression relative to UT cells for genes associated with this process in WT and mutant CADM1 (453-amino acid isoforms).
