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. Author manuscript; available in PMC: 2024 Apr 12.
Published in final edited form as: Sci Transl Med. 2023 Sep 20;15(714):eadi7244. doi: 10.1126/scitranslmed.adi7244

Fig. 4. TBL1XR1::TP63 fusion rewires enhancers to regulate gene expression.

Fig. 4.

(A) GSEA plots of indicated gene sets in SMZ1 cells expressing shTP63 versus shSeed control. Normalized enrichment score (NES); FDR: false discovery rate (FDR). (B) Venn diagram showing genes regulated by TBL1XR1::TP63 from RNA-seq in SMZ1 and genes bound by TBL1XR1::TP63 from ChIP-seq in SMZ1. (C) Pie graph showing the locations of TBL1XR1::TP63 binding peaks based on ChIP-seq of SMZ1 and DL40 cells. (D) Schematic of IP-MS of flag-tagged TP63, ΔNp63, TBL1XR1::TP63, TBL1XR1, and the truncated TBL1XR1 (ΔTBL1XR1). (E-G) IP using anti-TP63 antibody that binds TBL1XR1::TP63 in Cas-SMZ1-sgwtTP63 cells (E), anti-KMT2D antibody in SMZ1 cells and Cas9-SMZ1-sgwtTP63 cells (F), and anti-TP63 in SMZ1 cells and OCI-Ly12 cells (G). (H) IP of KMT2D in SMZ1 cells with 150 mM NaCl (low-salt) IP buffer or 300 mM NaCl (high-salt) IP buffer then immunoblotted for TP63. (I) Analysis of TBL1XR1::TP63-bound enhancers from HiChIP and ChIP-seq. (J) Analysis of PRO-seq signal at the genes associated with TBL1XR1::TP63-bound enhancers in Cas9-SMZ1-sgwtTP63 cells with or without TP63 fusion knockdown using Dox-inducible shRNA. PRO-seq signal is shown as violin plots of summed reads from the TSS to +75nt. P-value is from Wilcoxon test. (K) Motif analysis at TBL1XR1::TP63-bound enhancers by using HOMER.

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