Extended Data Fig. 4: WNTinib reduces EZH2 phosphorylation to drive the suppression of essential gene networks in CTNNB1-mutated HCC.
a, Heat maps and average profile plots for MYC-CTNNB1 tumor organoids (right) or MYC-Tp53 tumor organoids (left) displaying CUT&RUN H3K27me3 signal around the TSS/TES ( + /- 3 kb) of genes unchanged by WNTinib in the MYC-CTNNB1 tumor organoids (RNAseq – 7 days; N = 3767). Genes were chosen for similar expression levels to WNTinib-modulated genes. b, As in a, but displaying H3K27me3 levels at genes belonging to the Multicellular Organism Development Pathway in WNTinib-treated MYC-CTNNB1 tumor organoids. c, Representative genome browser tracks of H3K27me3 levels in WNTinib-treated MYC-CTNNB1 tumor organoids. Top: examples belong to Wnt Signaling Pathway; Bottom: example of a housekeeping gene. d, ChIP-qPCR enrichment of H3K27me3 at the promoters of genes shown in panel c. MYC-CTNNB1 tumor organoids were treated with DMSO, sorafenib (10 μM), or WNTinib (1 μM) for the indicated times. N = 3 independent experiments [mean, SEM]. P values; Sox7 *.00698 (1 day), *.0085 (3 day), *.01045 (7 day); Wnt11 *.02699 (1 day), *.02624 (3 day), *.02432 (7 day); Wnt7a *.01741 (1 day), *.01263 (3 day), ***.00045 (7 day); as calculated with two-tailed paired t-tests. Extended data associated with Fig. 2.
