Fig. 4: ETV6-RUNX1 binds DNA through the Runt domain, competing with native RUNX1.

a Integrative Genomics Viewer (IGV) screenshots of RUNX1 and ETV6-RUNX1 binding and DNase1 hypersensitivity (DNaseHS) in NALM-6 at the RUNX1 and SPI1 loci. R139G: loss-of-function point mutation in the Runt domain of ETV6-RUNX1. ΔHLH: deletion of helix-loop-helix pointed domain of ETV6-RUNX1. CTL: V5 ChIP in NALM-6 lacking V5-tagged protein. b Heatmaps showing ChIP-seq signal across all identified RUNX1/ETV6-RUNX1 binding sites in a 3 kb window centered on peak summits. c Dotplot of CPM for RUNX1 vs ETV6-RUNX1 ChIP. Colors show peaks classified as more highly bound by RUNX1 (R1), ETV6-RUNX1 (ER) or similarly bound by both (R1_ER). d Bar plot showing enrichment of GO-terms relating to cell cycle in genes mapped to R1_ER peaks as classified in (c). e Heatmaps showing ChIP-seq signal across all identified RUNX1/ETV6-RUNX1 binding sites in a 3kb window centered on peak summits for FLAG-RUNX1b IP in the presence of competing ETV6-RUNX1 or R139G (left) or V5-ETV6-RUNX1 IP in the presence of competing RUNX1b or Vector control. f IGV screenshots of RUNX1 and ETV6-RUNX1 binding and H3K27ac signal in NALM-6 expressing ETV6-RUNX1 or R139G for three of the most highly differential sites for H3K27ac. g Volcano plot showing H3K27ac differences, as determined by Wald test implemented in DiffBind⁶⁶, comparing ETV6-RUNX1 expressing NALM-6 to R139G controls across RUNX1 and ETV6-RUNX1 binding sites. Barplot shows number of significantly up- and down-regulated peaks. h Proportion of peaks classified as R1, ER or R1_ER (as in (c)) ranked from the most significantly down-regulated to the most significantly up-regulated and divided into 11 bins with equal numbers of peaks. Source data are provided as a Source Data file.