The genome wide mapping of H3K9 and H3K23 acetylation in Moz+/+ and Moz-/- MOZ-TIF2 AML cells

Monocytic leukemia Zinc finger protein (MOZ) is a MYST-type acetyltransferase involved in chromosomal translocation in acute myelogenous leukemia (AML) and myelodysplastic syndrome. MOZ is established as essential for hematopoiesis; however, the role of MOZ in AML has not been addressed. We propose that MOZ is critical for AML development induced by MOZ-TIF2 fusions. Moz-deficient hematopoietic stem/progenitor cells (HSPCs) expressing MOZ-TIF2 could form colonies in vitro but could not induce AML in mice. By contrast, Moz was dispensable for colony formation by HOXA9-transduced cells and AML development caused by HOXA9 and MEIS1, suggesting a specific requirement for MOZ in AML induced by MOZ/MLL-fusions. Expression of the of Meis1, but not Hoxa9, was reduced in Moz-deficient MOZ-TIF2 AML cells. AML development induced by MOZ-TIF2 was rescued by introducing Meis1 into Moz-deficient cells carrying MOZ-TIF2. Meis1 deletion impaired MOZ-TIF2­-mediated AML development. Active histone modifications were also severely reduced at the Meis1 locus in Moz-deficient MOZ-TIF2 AML cells. These results suggest that endogenous MOZ is critical for MOZ-fusion-induced AML development and maintains active chromatin signatures at target gene loci. Overall design: Chromatin immunoprecipitation DNA sequencing (ChIP-Seq) of genome wide H3K9 and H3K23 acetylation in Moz+/+ and Moz-/- MOZ-TIF2 AML cells