Extended Data Fig. 1: tRCCs display activation of OXPHOS programmes.

a, Source of H3K27ac ChIP-Seq data for ccRCC or tRCC cell lines analysed in this study. b, H3K27ac signal (quantified by ROSE2, Methods) at enhancers in proximity to OXPHOS genes in ccRCC and tRCC cell lines. c, Heatmap showing H3K27ac signal (quantified by ROSE2) at ETC and TCA cycle genes in tRCC vs. ccRCC cell lines. d, Normalized cell proliferation of ccRCC and tRCC cells in glucose or galactose media. Data are shown as mean -+ s.d. for n = 4 biological replicates per cell line except FU-UR-1 (n = 3) in glucose condition. e, Quantification of clonogenic capacity of ccRCC and tRCC cells under normoxic or hypoxic conditions. Data are shown as mean -+ s.d. for n = 3 (normoxia: 786-O, FU-UR-1. hypoxia: A498, FU-UR-1) and n = 4 (normoxia: Caki-1, A498, RCC4, Caki-2, KRMC-1, UOK109, s-TFE. hypoxia: 786-O, Caki-1,RCC4, Caki-2, KRMC-1, UOK109, s-TFE) biological replicates per cell line. f, Representative well for colony formation assay of ccRCC and tRCC cultured under normoxic or hypoxic conditions. g, OXPHOS gene signature scores in ccRCC, chRCC and tRCC tumours in the TCGA cohort. Centre line, median; box limits, upper and lower quartiles; whiskers, 1.5 times the interquartile range. h, OCR after the addition of oligomycin, FCCP, or antimycin A/rotenone in a chRCC cell line (UOK276) and a tRCC cell line (FU-UR-1). Data are shown as mean -+ s.d. for n = 16 (UOK276) and n = 13 (FU-UR-1) biological replicates. i, OCR after the addition of oligomycin, FCCP, or antimycin A/rotenone in an FH-RCC cell line (UOK262). Data are shown as mean -+ s.d. for n = 16 biological replicates. For (d-e), statistical significance was determined by two-tailed Student’s t-test. For (g), statistical significance was determined by two-sided Mann–Whitney test.