NUP98-fusion proteins regulate the expression and bind the promoter of Cdk6. (A) Pie chart of HA-NUP98/JARID1A chromatin binding events (%) in the indicated chromatin contexts. (B) Signal distribution of HA-NUP98/JARID1A normalized to the input signal, between the TSS and transcription end sites (TES) ± 3 kb up- and downstream. (C) Heat map showing HA-NUP98/JARID1A chromatin binding within ± 3 kb of annotated TSS. All annotated murine genes are plotted on the y-axis. (D) Representative ChIP-seq tracks showing the binding of HA-NUP98/JARID1A within the Hoxa cluster (top) and the promoter region of Meis1 (bottom). (E) Venn diagram showing the overlap of genes with NUP98/JARID1A-occupied promoter regions, all downregulated genes upon repression of NUP98-fusion proteins, and all genes that are highly overexpressed in NUP98-fusion–protein-driven mouse models. (F) Western blot analysis of CDK6 levels in bone marrow of mice transplanted with leukemia cells expressing different NUP98-fusion proteins, compared with bone marrow of wild-type (WT) mice. (G) Expression kinetics of Cdk6 in ex vivo–derived leukemia cells from the bone marrow upon Dox-mediated repression of the indicated NUP98-fusion proteins (mean ± SD; n = 3). (H) Western blot analysis of CDK6 levels of in vitro cultured NUP98/JARID1A-driven leukemia cells at indicated time points during Dox-mediated fusion protein repression (0.5 µg/mL). (I) Representative ChIP-seq tracks showing the binding of indicated NUP98-fusion proteins within the promoter region of Cdk6. *P < .05, **P < .01, ***P < .001, ****P < .0001.