GRID-seq reveals extensive remodeling of enhancer-promoter connections in RUNX1^R320∗ cells. (A) Representative heat map of the GRID-seq data set detecting RNA association with DNA regions across chromosome 21, only interactions within chromosome 21 are shown. (B) Z-score of detected RNA-DNA interactions classified as local, cis, and trans. Local interactions represent nascent RNA interactions with the gene body, cis interactions are within the same chromosome and outside the gene body region, and trans interactions are interchromosomal. (C) RNA-DNA interaction density across distance after log transformation, demonstrating the power law model of DNA looping and interaction described by Lieberman-Aiden et al (D) Enhancer-promoter interactions identified solely in either RUNX1 wild-type (WT) or RUNX1^R320∗ (R320∗) cells or present in both (shared), as detected by GRID-seq. (E) Motif analysis of RUNX1^R320∗ regulated enhancer and promoter regions in (D) selected significantly enriched motifs shown. (F) Normalized read counts of forkhead box gene expression in K562 RUNX1 wild-type and RUNX1^R320∗ cells via RNA-seq. Each bar represents the mean of 3 replicates and standard deviation. FOXK1 and FOXK2 subfamilies were measured against the remaining FOX subfamilies using 1-way ANOVA. ∗ P ≤ .05; ∗∗ P ≤ .01; ∗∗∗ P ≤ .001; ∗∗∗∗ P ≤ .0001.