Screening for epigenetic modulators identifies novel MEIS1 regulators in AML cells. (A) eGFP intensity values from monoclonal UB3 cells upon DOT1L CRISPR knockout are plotted on the y-axis (n ≥ 5000). Biological duplicates indicate independent sgRNAs. (B) Plot illustrating categories of chromatin modulators included in the CRISPR library design; the numbers indicate different genes under the category and the size of the bubble is proportional to the gene set size. Controls refer to pan-essential genes. (C) Strategy for phenotypic pooled CRISPR screening of epigenetic regulators for MEIS1 expression in the UB3 cell line. (D) Sorted gene hits based on differential beta scores for the eGFP-MEIS1 low minus eGFP-MEIS1 high fractions. Beta scores were calculated using MAGeCKFlute and plotted against rank of the genes on y-axis. Genes marked in red are potential MEIS1 activators while those in blue are candidate repressors. (E) Annotated protein complexes comprising top candidate hits identified in the epigenetic screen as identified using STRING database analysis. Hits from the epigenetics CRISPR library screen are marked with a glowing hue.