SGF29 is required for the survival of MEIS1/HOXA upregulated leukemias. CALM- and MLL-rearranged leukemias bind the H3K79 methyltransferase DOT1L and its partner proteins to increase H3K79 methylation across different target gene loci. SGF29 recognizes H3K4 trimethylation, a mark most enriched at gene promoters, through its Tudor domains and recruits the SAGA and ATAC complexes to increase histone H3 lysine acetylation onto target gene loci. This causes increase in downstream gene expression of pro-leukemic genes (including MEIS1). Knockout (KO) of SGF29 prevents SAGA/ATAC complex accumulation at target loci and the subsequent reduction in leukemogenic gene expression results in death of leukemia cells.