Fig 2: Schematic illustration of ARV-825 treating gastric cancer. (A) Technical roadmap of ARV-825 treating gastric cancer. (B) Schematic diagram of ARV-825 degrading BRD4. (C) Molecular mechanism of ARV-825 treating gastric cancer. Ub, ubiquitin; E2, ubiquitin-conjugating enzyme; cereblon, E3 ubiquitin ligase; Ac, acetylation modification site.

Fig 3: A The Hi-C data analysis of super-enhancer regions and promoter of LYL1 in THP-1 cell line (track 1) represents interaction at the LYL1 gene loci, and the ChIP-seq gene tracks (track 2–15) represent the H3K27ac signal in AML cell lines (NB4, MV4–11, and THP1) and 11 AML samples at the LYL1 gene loci. The super-enhancers are shown as green boxes. B The public BRD4 ChIP-Seq data of AML cell line MV4–11 (GSE101821) showed that the gene region of LYL1 had coincident signals (track 1). The ChIP-seq gene tracks represent the H3K27ac signal in NB4 cells (track 2) and NB4 cells treated with GNE-987 (25 nM, 24 h) (track 3) at the LYL1 gene loci. The reads signal of RNA-Seq in NB4 cells (track 4–5) and NB4 cells treated with GNE-987 (25 nM, 24 h) (track 6–7) at the LYL1 gene loci. C Western blotting showed that LYL1 level was significantly decreased in NB4 cells treated with GNE-987 (0, 1, 2, 6, 12 nM, 24 h). D Western blotting showed that LYL1 level was significantly decreased in Kasumi-1 cells treated with GNE-987 (0, 1, 2, 6, 12 nM, 24 h). E qPCR showed that LYL1 was significantly downregulated in NB4 cells treated with GNE-987 (0, 1, 2, 6, 12 nM, 24 h). F qPCR showed that LYL1 was significantly downregulated in Kasumi-1 cells treated with GNE-987 (0, 1, 2, 6, 12 nM, 24 h). G expression pattern of LYL1 between AML patients and healthy controls in public transcriptomic dataset (GSE114868)

Fig 4: BRD4 occupancy at different chromatin regions of HCCLM3 cells is perturbed after AZD5153 exposure. (A–C) ChIP analysis of BRD4 and H3K27Ac occupancy at the promoters, gene bodies and super-enhancer (SEs) in HCCLM3 cells treated with DMSO or AZD55153 (10 μM) for 24 h (D–G) Average signal intensity plot of BRD4 and H3K27Ac binding to all peaks, promoters, gene bodies and SEs in the genome of control and AZD5153-treated HCCLM3 cells. The 0bps denote transcription start sites (TSSs) and the regions upstream and downstream of TSS are denoted by−and +, respectively.

Fig 5: BRD4 is amplified and/or upregulated in OC(A) BRD4 alteration was examined in tumor samples using cBioPortal (www.cbioportal.org). BRD4 alterations occurred most commonly in ovarian cancer, shown by the alteration frequency in TCGA. Amplifications (red) were the most common alteration. (B) BRD4 mutations detected in TCGA tumors are shown. (C) BRD4 alterations including mutations, copy number, mRNA expression in TCGA OC dataset are shown. (D) Overall survival based on BRD4 alterations in TCGA OC is shown. (E) Mutual exclusivity of BRD4 alteration from TCGA data analysis among genes involved in OC.