Extended Data Fig. 8: ChIPseq of Menin and MLL1 in MEN1-WT and -M327I-mutant cells.
From: MEN1 mutations mediate clinical resistance to menin inhibition
a) ChIPseq tracks of Menin and MLL1 at the PBX3, MEF2C, JMJD1C-loci and the HOXA-cluster in MV4;11 cells under revumenib treatment (representative example of 3 replicates). b) Torpedo-plots of total Menin signal intensity around transcription start sites (TSS) from ChIP-sequencing (ChIPseq) in OCI-AML3-MEN1-WT and -M327I-mutant cells treated with revumenib (0.1μM, 1μM) or DMSO as control (N = 2). Shown is one representative example. c) ChIPseq tracks of Menin at the MEIS1, PBX3, MEF2C, JMJD1C-loci and the HOXA-cluster in OCI-AML3 cells under revumenib treatment. d) Bar graphs showing Menin-ChIP-qPCR results at the MEIS1, MEF2C and HOXA10 transcription start sites after treatment with 100nM revumenib or DMSO as control (4 days treatment) (N = 3, mean +/− SD). An unpaired, two-tailed t-test was used for statistical analysis. e) Torpedo-plots of Menin signal intensity around TSS from ChIPseq in MEN1-WT and -T349M-mutant PDX3 treated with VTP-50469 for 14 days. f) Menin-TSS-signal at MLL1-target genes in PDX3 (mean +/− SD, 3000 TSS data points per condition). Two-tailed Mann-Whitney-Tets was used for statistical analysis. g) Read-normalized MLL1-TSS-signal at sites that lose >80% of Menin in WT cells treated with VTP-50469 (mean +/− SD, 293 data points per condition). Two-tailed Mann-Whitney-Tets was used for statistical analysis. h) ChIPseq tracks of Menin and MLL1 at the MEIS1-locus and HOXA-cluster in PDX3.
