HSPCs isolated from bone marrow cells of Trp53-/- mice were transfected with retroviruses encoding shKmt2d or shRen. 48 hours later, GFP-positive cells were sorted by a BD FACSAria™ III Cell Sorter (BD Biosciences).  Genome sequencing was performed using an Illumina NovaSeq 6000 sequencing platform. CUT&Tag library construction Kmt2d knockdown and Kmt2d restored AML cells with doxycycline withdrawal for 4 days were harvested for CUT&Tag assay using NovoNGS® CUT&Tag 3.0 High-Sensitivity Kit (N259-YH01-01A, NovoProtein, Suzhou, China).