Enhancer hypomethylation and activation is associated with increased target gene expression in CN-AML patients. (A) DNA methylation fold change between progenitors and CN-AML at hypomethylated CAGE enhancers that show no change or gain H3K27ac. (B) Gene expression of enhancer target genes in CN-AML relative to NBM shows increased expression relative to NBM. This increased expression is significantly greater at target genes of hypomethylated enhancers that show increased H3K27ac (Student t test P ≤ .01). (C-D) CRISPR-cas9 deletion of 2 candidate enhancers showing reduced trend of target gene expression in homozygous deletion clones (blue squares) relative to wild-type clones (red circles) of target genes in KG1a cells. A.U., arbitrary unit; n.s., not significant; WT, wild-type.