Fig. 7 | Nature Communications

Fig. 7

From: Analysis of chromatin accessibility uncovers TEAD1 as a regulator of migration in human glioblastoma

Fig. 7

TEAD1 regulates GBM migration by modulating AQP4 expression. a Venn diagram depicts the intersection of genes with TEAD motifs and genes consistently downregulated in TEAD1KO cell lines and migration-deficient spheroids (striped area). AQP4 is the only one of 32 genes in this intersection found to be a direct TEAD1 binding target in vivo (highlighted in red). ATAC-seq set contains 2612 peak-annotated genes from E+GSC vs. E−GBM+NSPC differential accessibility analysis. Top RNA-seq set (overall targets) contains all 1648 significantly up or downregulated genes from TEAD1KO vs. Sham differential expression analysis in all samples from four different patient-derived GBM lines and three migration experiments (n = 7; padj. < 0.05; all log2(fold change) values of HGNC-annotated genes included). Bottom RNA-seq set (migratory targets) contains 865 significantly up or downregulated genes from TEAD1KO vs. Sham G-13063 spheroids from three independent migration experiments (n = 3; padj. < 0.05; log2(fold change) >1 or <−1). See also Supplementary Fig. 7. b Spheroid migration assay showing significant reversal of cell dispersion deficit at 30 h in TEAD1 knockout cells after overexpression of CDH11 or AQP4 (G-13063 line; laminin + PDL substrate; n = 3 wells. TEAD1KO + CDH11OE: **p = 0.004; TEAD1KO + AQP4OE: **p = 0.0015. Bars represent mean ± SEM). On right, migration area marked by red dash line in representative spheroids is shown. Scale bar = 75 μM. c Quantification of AQP4 expression by RT-qPCR. AQP4 is significantly upregulated in TEAD1KO cells after TEAD1 overexpression (n = 6, 4 technical and 2 biological replicates; *p = 0.02 TEAD1KO + TEAD1OE vs. TEAD1KO) and is robustly expressed after exogenous lentivirus overexpression. Bars represent mean ± SEM

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