The p300/CBP recruitment induces excessive histone H3 lysine 27 acetylation (hyper-acetylation; H3K27ac) and creates unusually large topological domains (aka megadomains) in chromatin that enable aberrant gene transcription by sequestering transcriptional activators away from pro-differentiation genes12–17 and activating proliferation and anti-differentiation genes16–21, resulting in perpetual tumor cell growth. The gene discussed is EP300; the disease is neoplasm.