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. 2022 Oct 20;13(1):146–169. doi: 10.1158/2159-8290.CD-22-0416

Figure 5.

Figure 5. Enzymatic domain of UTX is dispensable for its tumor-suppressive functions in response to Menin-MLL inhibition. A, Schematic of UTX protein. Highlighted are the 8 tetratricopeptide repeats (TPR; 93–385 aa) and the histone demethylase (JmjC) domain (1,095–1,258aa). Three ∼500 amino acid long truncations are also represented. B, Growth competition assay in mouse UtxKO MLL-AF9 leukemia cells expressing different RFP-tagged Utx cDNAs and treated with Menin-MLL inhibitor (MI-503) for 2 or 6 days. The graph shows the relative growth of leukemia cells infected with RFP-tagged Utx cDNAs measured by flow cytometry (mean ± SEM, n = 3 infection replicates, P value calculated by Student t test). C, Principal component analysis (PCA) of gene-expression data from UtxKO MLL-AF9 leukemia cells expressing different RFP-tagged Utx cDNAs and treated with vehicle (DMSO) or Menin-MLL inhibitor (MI-503) for 96 hours. D, Cdkn2c expression (mean normalized read counts) from different Utx truncations in mouse MLL-AF9 leukemia and treated with vehicle (DMSO) or Menin-MLL (MI-503) for 96 hours (mean ± SEM, n = 3 replicates, P value calculated by Student t test).

Enzymatic domain of UTX is dispensable for its tumor-suppressive functions in response to Menin–MLL inhibition. A, Schematic of UTX protein. Highlighted are the 8 tetratricopeptide repeats (TPR; 93–385 aa) and the histone demethylase (JmjC) domain (1,095–1,258aa). Three ∼500 amino-acid-long truncations are also represented. B, Growth competition assay in mouse UtxKO MLL-AF9 leukemia cells expressing different RFP-tagged Utx cDNAs and treated with Menin–MLL inhibitor (MI-503) for 2 or 6 days. The graph shows the relative growth of leukemia cells infected with RFP-tagged Utx cDNAs measured by flow cytometry (mean ± SEM, n = 3 infection replicates, P values calculated by Student t test). C, Principal component analysis (PCA) of gene expression data from UtxKO MLL-AF9 leukemia cells expressing different RFP-tagged Utx cDNAs and treated with vehicle (DMSO) or Menin–MLL inhibitor (MI-503) for 96 hours. D,Cdkn2c expression (mean normalized read counts) from different Utx truncations in mouse MLL-AF9 leukemia cells treated with vehicle (DMSO) or a Menin–MLL inhibitor (MI-503) for 96 hours (mean ± SEM, n = 3 replicates, P values calculated by Student t test).