Extended Data Fig. 11: Lineage factor dependent MYC expression in normal renal epithelial cells.
From: The renal lineage factor PAX8 controls oncogenic signalling in kidney cancer
a. Fluorescence in situ hybridisation in one nucleus of 786-M1A cells (representative image, N = 4). Blue, DAPI staining; green, chromosome 8q telomere; orange MYC 5’. b–c. ATAC-seq tracks overlapped for 786-M1A cells upon HNF1B depletion. shRen, N = 5; shHNF1B, N = 6. d. Inhibitory effect of PAX8 depletion on chromatin accessibility at the enhancers in the MYC locus. Fold changes and adjusted two-sided p-values derived by DESeq2. e. Competitive proliferation assay against shRen control cells in HK2 cells. Data points, technical replicates (N = 3), standard deviation. Two-sided Kruskal-Wallis test. f–j. Relative mRNA expression as determined by qRT-PCR. Data points, independent RNA preps (N = 3). Mean and SEM. Two-sided Kruskal-Wallis test. k. Summary. PAX8 is required for tissue-specific oncogenic programmes by integrating signals from inherited and acquired genetic alterations: inactivating mutations in VHL and the common ccRCC predisposition SNP rs7948643 upstream of CCND1, as well as metastasis-associated 8q21.3-q24.3 amplifications upstream of MYC, which co-opt the physiological PAX8-HNF1B program that supports MYC expression in proliferating normal renal epithelial cells.
