TSS distal hypomethylation and enhancer activation occurs at both CD34⁺poised enhancers and de novo CN-AML enhancers. (A) Identification of hypomethylated TSS distal DMCs occurring in H3K4me1 ChIP-seq peaks from the epigenome of CD34⁺ cells, CN-AML samples, or both. (B) The percentage of H3K4me1-positive hypomethylated TSS distal DMCs displaying increased average H3K27ac ChIP-seq signals in CN-AML relative to CD34⁺ cells. (C) Example of a poised CD34⁺ enhancer region that becomes activated in association with increased H3K27ac. (D) A de novo established AML-specific enhancer in the AML epigenome at a hypomethylated TSS distal DMC showing gain of H3K4me1 and H3K27ac.