Figure 4.
UBTF-TD genomic localization is required for gene activation. (A) Experimental design of FKBP12F36V-HA-UBTF-TD genomic occupancy experiment. (B) Tornado plots depicting the merged genomic occupancy (n = 3 replicates) at significantly depleted HA: FKBP12F36V-HA-UBTF-TD target regions (n = 266 regions, FDR < 0.5) after treatment with dTAG-13 for 3 days. Occupancy for KMT2A and menin are also shown. (C) Heatmap of the top depleted regions and their closest genes (n = 29). Heatmap colors depict row normalized enrichment. (D) Genomic tracks of merged coverage (n = 3) of HA: FKBP12F36V-HA-UBTF-TD cells treated with DMSO (black) or dTAG-13 (red) for HA, KMT2A, menin, H3K27ac (27ac), or H3K4me3 (me3). (E) Volcano plot of differentially expressed genes in FKBP12F36V-HA-UBTF-TD cells treated with DMSO or dTAG-13. Top targets (29 genes from panel C) are annotated in red. (F) mRNA levels of top target genes from panel C as compared with nontargets. (G) Upstream regulator analysis from ingenuity pathway analysis. Top targets from panel B were used for the prediction. FDR, false discovery rate; DMSO, dimethyl sulfoxide.