Fig. 3: SMARCA4/2 regulate ITPR3 transcription through remodeling chromatin accessibility at its gene locus. | Nature Communications

Fig. 3: SMARCA4/2 regulate ITPR3 transcription through remodeling chromatin accessibility at its gene locus.

From: SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria

Fig. 3

a Venn diagram of Ca2+-related genes from Fig. 2a, b that are enriched in SCCOHT-1 and BIN-67 cells with SMARCA4 restoration. b Heatmap of Ca2+-related genes bound by SMARCA4 (n = 69) in indicated SCCOHT (SCCOHT-1 and BIN-67) and NSCLC (H1299) cell lines with SMARCA4/2 restoration. Left: normalized reads from RNA-seq data of BIN-67 and SCCOHT-1 cells with SMARCA4 restoration49. Middle: normalized reads from RNA-seq data of BIN-67 cells with SMARCA4/2 restoration60. Right: normalized signal from microarray data of H1299 cells with SMARCA4 restoration61. Row scaling was used to generate the heatmap. The last column represents changes of genes in H1299 cells ± SMARCA4 restoration: ns not significant, up upregulated, down downregulated. c RT-qPCR measurements of ITPR3 mRNA expression in indicated SCCOHT and NSCLC cell lines with SMARCA4/2 restoration. GAPDH was used for normalization. Mean ± SD, n = 3 (BIN-67, SCCOHT-1, H1299) or 4 (H1703) independent experiments, one-way ANOVA followed by Dunnett’s test for multiple comparisons to the control group (BIN-67, SCCOHT-1, H1703) or two-tailed t-test (H1299), p values (p): BIN-67, all <0.0001; SCCOHT-1, A2—0.0004, A4—0.0001; H1299—0.0318; H1703, A2—0.0097, A4—0.0013. d Immunoblots of indicated proteins in indicated SCCOHT and NSCLC cell lines ± SMARCA4/2 restoration. e SMARCA4 occupancy in vicinity of the ITPR3 locus assessed by chromatin immunoprecipitation sequencing (ChIP-seq) in indicated SCCOHT and lung cancer cell lines ± SMARCA4 restoration. SMARCA4 in H1299 cells was induced by doxycycline (Dox)61. Track height is normalized to relative number of mapped reads. f Chromatin structure changes in vicinity of the ITPR3 locus assessed by H3K27Ac ChIP-seq and assay for transposase-accessible chromatin sequencing (ATAC-seq) in indicated SCCOHT and lung cancer cell lines ± SMARCA4/2 restoration. Track height is normalized to relative number of mapped reads. a–f Ctrl control, A4 SMARCA4, A2 SMARCA2. *p < 0.05, **p < 0.01, ****p < 0.0001.

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