CBFb-SMMHC inhibition triggers apoptosis by disrupting MYC chromatin dynamics in acute myeloid leukemia [ATAC-seq]

We recently reported the discovery of a small molecule inhibitor, AI-10-49 which can specially inhibit the protein-protein interaction between RUNX1 tumor suppressor and CBFβ-SMMHC oncogene. We also demonstrated that AI-10-49 can re-establish the RUNX1 transcriptional program in inv(16) cells and can extend the survival of inv(16) leukemic mice. To identify the changes in chromatin accessibility associated with AI-10-49, we performed ATAC-seq analysis in ME-1 cells [human inv(16) leukemia cell line] treated with AI-10-49. ME-1 cells were treated with DMSO/ AI-10-49 (1uM) for six hours and cells were tagmented using Tn5 transposase. DNA libraries were sequenced using 100bp paired end reads on an Illumina HiSeqTM 2000. Two independent experiments were conducted for DMSO as well as AI-10-49 treatments.