CBFb-SMMHC inhibition triggers apoptosis by disrupting MYC chromatin dynamics in acute myeloid leukemia [ChIP-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 CBFß-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 epigenetic changes as well as RUNX1 binding associated with AI-10-49, we performed genome wide analysis of H3K27ac histone mark as well as RUNX1 bindings in ME-1 cells [human inv(16) leukemia cell line] treated with AI-10-49. Overall design: ME-1 cells were treated with DMSO/ AI-10-49 (1uM) for six hours, crosslinked chromatin was immunoprecipitated with H3K27 acetylation and RUNX1 antibodies. DNA libraries were sequenced using 50bp single end reads on an Illumina HiSeqTM 4000.