dox  (MedChemExpress)

Journal: bioRxiv

Article Title: MYST acetyltransferases are a targetable therapeutic vulnerability in SETBP1-mutant leukemia

doi: 10.64898/2026.01.08.697228

Figure Lengend Snippet: A. Plot of fold enrichment of mean biotinylated protein abundance derived from four replicates per condition. Plot represents the enrichment of peptides from control vector-BirA*, SETBP1 WT -BirA*, and SETBP1 D868N -BirA*. The x-axis of the presented plot shows the fold enrichment in SETBP1 WT versus control. The y-axis of the plot shows fold enrichment in SETBP1 D868N versus control. Dashed lines represent a fold enrichment value of 2. B. Network of proteins identified in SETBP1 WT -BirA* or SETBP1 D868N -BirA* versus Control-BirA* transduced K562 cells. Proteins with >2-fold enrichment over BirA alone in either of the SETBP1 conditions were analyzed using STRING, a physical interaction network. Clusters were identified using DBScan, and enriched terms within a cluster are indicated by the labels. The color of the nodes represents the identified pathways to which the proteins belong to as described in the figure. Proteins involved in chromatin biology are highlighted by color—green: histone methyltransferase, pink: super elongation complex, yellow: histone acetyltransferase, blue: bromodomain proteins. C. Heatmap of normalized intensity for key proteins identified in BioID in SETBP1 WT -BirA* or SETBP1 D868N -BirA* versus Control-BirA* transduced K562 cells as prioritized in the network shown in (B). Four replicates are shown for each condition. D. Validation of hits from the screen by streptavidin (SA) pulldown followed by immunoblot with the indicated antibodies in K562 cells expressing SETBP1 WT -BirA* or a BirA* control. E . Co-immunoprecipitation of V5-tagged control or V5-tagged-SETBP1 in HEK293 cells. The V5 antibody was used for immunoprecipitation, followed by immunoblots with antibodies against the indicated putative SETBP1-interaction partners. F. Co-immunoprecipitation of BRPF1 and KAT7 in control (-DOX) and SETBP1 D868N -induced (+ DOX) conditions in K562 cells demonstrates enhanced interaction of KAT7 and BRPF1 in SETBP1 D868N -expressing cells . G. Proposed model of MYST complex interaction with SETBP1.

Article Snippet: Doxycycline (DOX) inducible K562 (CCL-243 ATCC) cells were generated by lentivirus transduction.

Techniques: Quantitative Proteomics, Derivative Assay, Control, Plasmid Preparation, Biomarker Discovery, Western Blot, Expressing, Immunoprecipitation

Journal: bioRxiv

Article Title: MYST acetyltransferases are a targetable therapeutic vulnerability in SETBP1-mutant leukemia

doi: 10.64898/2026.01.08.697228

Figure Lengend Snippet: A. CUT&RUN for SETBP1 in K562 cells with a doxycycline (DOX)-inducible construct in triplicate. Heatmaps and median signal profiles of normalized SETBP1 CUT&RUN signal in control (no DOX) and SETBP1 D868N -induced (+DOX) conditions. The signal is shown at peak centers +/- 3kb. Each row in the heatmap represents one SETBP1 binding region. B. Top motifs identified by HOMER at SETBP1-bound regions. The q-values represent Benjamini-Hochberg corrected p-values calculated by HOMER. Percentages indicate the fraction of sequences in target or background regions that contain each motif. Motifs with q-value<0.0001 were ranked in descending order by percentage of target regions (SETBP1 peaks) containing the motif, and the top five are shown. C. Spearman correlation of SETBP1, KAT7, and KMT2A signal in SETBP1 D 868 N -induced condition. SETBP1 has a high degree of correlation with KAT7. D. Venn diagram of SETBP1 and KAT7 binding regions in the SETBP1 D 868 N -induced condition. There are 841 regions bound by SETBP1 only, 16600 regions bound by KAT7 only, and 1579 regions co-occupied by both SETBP1 and KAT7. E. Normalized signal tracks for SETBP1, KAT7, and IgG control at MECOM , MYB , and STAT5B loci in the SETBP1 D868N -induced condition.

Article Snippet: Doxycycline (DOX) inducible K562 (CCL-243 ATCC) cells were generated by lentivirus transduction.

Techniques: Construct, Control, Binding Assay

Journal: bioRxiv

Article Title: MYST acetyltransferases are a targetable therapeutic vulnerability in SETBP1-mutant leukemia

doi: 10.64898/2026.01.08.697228

Figure Lengend Snippet: A. Genomic feature distribution for peaks in SETBP1, KAT7, and shared (co-occupied) regions in SETBP1 D 868 N -induced condition (K562 cells). Approximately 50% of the shared regions overlap with promoter regions. B. Top 20 Gene Ontology (GO) Molecular Function (MF) terms from over-representation analysis of SETBP1 D 868 N upregulated genes (padj<0.05) based on RNAseq data. GO terms were selected based on adjusted p-value and ordered by gene ratio for visualization. Gene ratio indicates the proportion of input upregulated genes in each GO term (intersect) relative to the total input upregulated genes (query). Term size represents the total number of genes annotated to each GO term. Color reflects the adjusted p-value of functional enrichment.

Article Snippet: Doxycycline (DOX) inducible K562 (CCL-243 ATCC) cells were generated by lentivirus transduction.

Techniques: Functional Assay