WT1 mutation induces DNA hypermethylation of PRC2 target genes. (A-B) Summary and examples of gene sets enriched in the set of WT1mut-associated hypermethylated genes (WT1me) derived from Boolean implications from the TCGA data. Gene sets were obtained from the MSigDB. Hypergeometric test P values are indicated, and enrichment plots for selected gene sets are illustrated. (C-D) Summary and examples of gene sets enriched in the set of genes hypermethylated in THP1 cells engineered to express mutant WT1 (as in Figure 2F). Hypergeometric test P values are indicated and enrichment plots for selected gene sets are illustrated. (E) Venn diagram showing overlap of the WT1me genes from the TCGA data set and genes with high CpG content in their promoters. Overlap of these gene sets was measured by Fisher’s exact test (right tailed). The universe of genes in the contingency table is equal to 15 880, which is the set of genes that were studied and classified as having high or low CpG content.²⁹  (F) Venn diagram showing overlap of the WT1me genes from the TCGA data set and genes with WT1 DNA binding motifs in their promoters. Overlap of these gene sets was measured by Fisher’s exact test. (G) Comparison of PRC2 target gene enrichment among hypermethylated genes associated with individual AML mutations from the TCGA data set. The y-axis shows the negative log of the P value of the cooccurrence between the H3K27me3 Benporath gene set and methylated genes derived from HI-HI Boolean implications for each recurrent mutation. Overlap of the gene sets was measured by Fisher’s exact test (right tailed).