In this study, we develop a single-cell CRISPR gene tiling pipeline “sc-Tiling” to provide high-resolution transcriptomic profiling of the coding regions of histone H3 lysine 79 (H3K79) methyltransferase DOT1L, an epigenetic therapeutic candidate selectively essential to mixed-lineage leukemia gene-rearranged (MLL-r) leukemia17–19. Here, DOT1L is linked to leukemia.