FIGURE 6

FIGURE 6

FOXD1 is a PRC2 target gene in melanocytes. (A) Scheme to identify melanocyte-specific PRC2 targets. (B) H3K27me3 (top) and RNA-seq (bottom) around the FOXD1 locus in melanocytes and fibroblasts. Rank indicates the rank of enrichment within the entire melanocyte genome ie, rank 7 is the seventh highest level of H3K27me3 enrichment in the melanocyte genome. (C) RNA-seq data of foxd1 (top) and foxd3 (bottom) levels within miniCoopR H3.3 and H3.3K27M zebrafish tumors. foxd1, p = 0.0397, L2FC = −1.33. foxd3, p = 0.101, L2FC = 0.656. (D) RNA-seq data of Foxd1 (top) and Foxd3 (bottom) levels in Ezh2 wild-type and Ezh2^fl/fl mouse tumors. Foxd1, p = 0.185, L2FC = 0.853. Foxd3, p = 4.49E-11, L2FC = 2.81. (E) qPCR data of FOXD1 (top) and FOXD3 (bottom) levels in A375 human melanoma cells treated with EZH2 inhibitor GSK-343. FOXD1, p = 0.0098, L2FC = 1.218. FOXD3, p = 0.0037, L2FC = 1.275. (F) Kaplan-Meier survival curves of Tg(mitfa:BRAF(V600E)); tp53^zdf1/zdf1; mitfa^w2/w2 zebrafish injected with indicated miniCoopR constructs. p value shown calculated from log-rank test between miniCoopR GFP and FOXD1. (G) qPCR data of foxd3 levels in miniCoopR (MC) GFP and FOXD1 tumors, p = 0.0011.