FIGURE 1

FIGURE 1

H3.3K9M suppresses melanoma formation. (A) The miniCoopR vector strategy overexpressing candidate genes in a melanocyte-specific fashion. Schematic adapted from Ceol et al. (2011). (B) Kaplan-Meier survival curves of Tg(mitfa:BRAF(V600E)); tp53^zdf1/zdf1; mitfa^w2/w2 zebrafish injected with indicated miniCoopR constructs (p value = 1.81e−06 calculated from log-rank test between miniCoopR H3.3 and H3.3K9M; 12 miniCoopR H3.3 and four H3.3K9M animals were censored from the study). (C) Western blot of acid-extracted histones from established tumors demonstrates a global loss of H3K9me3. (D) Top 1000 differentially expressed genes between miniCoopR H3.3 and H3.3K9M (sorted by p-value adjusted). (E) GSEA plots with enriched signatures in H3.3K9M tumors displaying enrichment for interferon responses. (F) Panther gene ontology analysis of the top 250 upregulated gene transcripts by p-value. (G) FishEnrichr analysis of the top 250 upregulated gene transcripts by p-value reveals neutrophil pathways among top 10 GO biological processes (Chen et al., 2013; Kuleshov et al., 2016). H, 16 of 19 transposable elements upregulated in H3.3K9M tumors.