Histone acetylation is key to regulating the transition of hematopoietic stem cells to myeloid lineage cells by adding nuance to the histone code required for recruiting chromatin binding proteins. We aimed at identifying how the MOZ acetylation complex is recruited to oncogenic loci in acute myeloid leukemia by conducting a domain focused CRISPR tiling screen for all canonical members of the complex. The strongest drop-out was the least studied subunit MEAF6, which is present in both the MOZ and HBO1 complexes. Previous research has established that the MYST family histone acetyltransferase complexes, MOZ and HBO1, are involved in driving and maintaining leukemogenesis. Moreover, certain of the histone marks that they regulate - H3K9ac and H3K14ac - facilitate the processivity of RNA polymerase II to upregulate expression of Hox cluster genes and oncogenes that disrupt stem cell differentiation and self-renewal potential. Knock-out of MEAF6 and its coiled-coil domain in AML cells demonstrated a strong proliferative defect and induction of differentiation. To our surprise, MEAF6-KO also nearly fully eliminated H3K9 and K14 acetylation compared to the minimal loss of histone acetylation upon KO of the catalytic subunits KAT6A and KAT7 in previous studies. This leads us to conclude that the small “accessory” subunit, MEAF6, plays a vital role in the assembly of these two HAT complexes.