Fig. 6 | Nature Communications

Fig. 6

From: Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma

Fig. 6

BET protein degrader destroys the core transcriptional programs in liposarcoma (LPS). a Differential responses of genes to OTX015 and ARV-825 treatment according to BET protein occupancy around their promoter-proximal regions in LPS141 cells. BET(+) denotes genes with at least one ChIP-seq peak of BET proteins within their promoter-proximal regions; BET(−) denotes genes that are negative for binding of BET proteins. b Differential responses of genes to OTX015 and ARV-825 treatment according to enhancer status in LPS141 cells. c Quantitative reverse transcription PCR (qRT-PCR) analysis showing the mRNA levels of core TF genes, SNAI2, and CDKN1A upon ARV-825 and OTX015 treatment (200 nM, 24 h) in LPS141 cells. CDKN1A was used as positive control for differentially expressed genes. d Immunoblot analysis showing the impact of ARV-825 and OTX015 (200 nM, 24 h) on levels of BET proteins, core TFs, and SNAI2 in LPS141 cells. e Differential responses of genes to OTX015 and ARV-825 treatment (200 nM, 24 h) according to their enhancer occupancy by FUS-DDIT3 in MLS402 cells. f qRT-PCR analysis showing the mRNA levels of FST, IL8, BCAT1, and CDKN1A upon ARV-825 and OTX015 treatment (200 nM, 24 h) in MLS402 cells. CDKN1A was used as positive control for differentially expressed genes. Data are presented as mean ± SEM; n = 3. g GSEA plots of Trabectedin response pathway in MLS402 cells treated with dimethyl sulfoxide (DMSO) versus ARV-825 or OTX015. h Models of BET protein-dependent core transcriptional programs in myxoid LPS (MLPS) and de-differentiated LPS (DDLPS). Depletion of BET proteins serves as a common strategy to target these core transcriptional dependencies. Box plots indicate median value (center line), first and third quartiles (box limits), as well as minimum and maximum values (whiskers) after excluding outliers (dots). Wilcoxon signed-rank test was applied for a, b, e; one-way analysis of variance (ANOVA) was applied for c, f. n.s., not significant; *p < 0.05; **p < 0.01; ***p < 0.001. Source data are provided as a Source Data file

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