Fig. 4: Arid1a ablation silences the enhancer of the A20 gene to stimulate NF-κB signaling. | Nature Communications

Fig. 4: Arid1a ablation silences the enhancer of the A20 gene to stimulate NF-κB signaling.

From: ARID1A loss induces polymorphonuclear myeloid-derived suppressor cell chemotaxis and promotes prostate cancer progression

Fig. 4

a Relative expressions of SWI/SNF components in epithelium from 12-week-old PtenPC−/− and PtenPC−/−; Arid1aPC−/− prostates (n = 3). b Heatmap of H3K27ac ChIP-seq in the differentially accessible sites obtained by ATAC-seq on Arid1a loss in Myc-CaP cells (± 2 kb regions centered at the peak summit). PC, peak center. c Heatmap of the ChIP-seq profiles of BRG1 peaks in control and Arid1a KO Myc-CaP cells shown in a horizontal window of ±2 kb from the peak center. d Profile and bar plot of BRG1 binding, H3K27ac modification and ATAC-seq intensities across BRG1 down peaks after Arid1a ablation. e ChIP-seq profiles for BRG1, H3K4me3, H3K4me1 and H3K27ac at the sites reducing BRG1 binding after Arid1a loss. f Venn diagram of the genes showing reduced BRG1 binding, accessibility and expression in Arid1a KO Myc-CaP cells compared to WT cells. g ChIP-seq tracks of BRG1, H3K27ac, H3K4me1, H3K4me3 and ATAC-seq signals in A20 gene loci as indicated. h ChIP-qPCR assays of BRG1, BAF155, ARID1A and ARID1B binding in the A20 enhancer (n = 3), ns, no significance. i IB analysis of the indicated protein in WT and Arid1a KO Myc-CaP cells with or without A20 enhancer activation (CRISPRa/dCas9-based induction) and/or TNFα stimulation. j IB analysis in WT and ARID1A overexpressing Myc-CaP cells with or without A20 enhancer suppression (CRISPRi/dCas9-based suppression) and/or TNFα stimulation. k Tumor volume of the mice inoculated with Myc-CaP expressing sgArid1a and control vector with or without A20 enhancer activation (WT/Arid1a KO + Ctrl-sgRNA and WT + Enhancer-sgRNA, n = 7 for each group; Arid1a KO + Enhancer-sgRNA, n = 5). a, d, h, k Data represent the mean ± SEM. Statistical significance was determined by two-tailed unpaired t-test (a, d, h) and two-way ANOVA followed by multiple comparisons (k). i, j Experiments were repeated three times independently with similar results; data from one representative experiment are shown. ns, no significance. Source data are provided as a Source Data file.

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