To identify if any functional domains within DNMT1 or DNMT3B are essential for viability, we performed CRISPR/Cas9 tiling screens in AML cell lines wild-type or mutant for DNMT3A. A pooled lentiviral library was generated to target the entire coding regions of both DNMT1 and DNMT3B (Fig. 2a), with non-targeting sgRNAs and sgRNAs targeting essential genes included as negative and positive controls, respectively (Fig. 2b). Here, DNMT3A is linked to acute myeloid leukemia.