Fig. 4

Transcriptional profiling analysis revealed a major action of CRTC1-MAML2 fusion in co-activating CREB target genes in human MEC cells. a Venn Diagram indicated that CREB knockdown in fusion-negative HSY and fusion-positive H3118 cells caused gene expression changes in distinct and common genes. Down-regulated and up-regulated genes were shown in green and red. b A heatmap of differential expressed genes in HSY and H3118 cells after shCREB transduction. Three biological replicates for each group were included in the analysis. c Venn Diagram indicated distinct and overlapping genes between fusion knockdown and CREB knockdown in H3118 cells. d A significant subset of CRTC1-MAML2 and CREB common-regulated genes showed CREB binding sites on their promoters. Comparison of the fusion/CREB-regulated genes and the gene set with CREB binding site in the promoter revealed 55.8 % of the fusion/CREB target genes contain CREB binding site. e Top 20 transcription factors whose target gene sets were enriched in down-regulated fusion knockdown H3118 array. Each gene set contains genes that shared a transcription factor-binding site defined in the TRANSFAC (version 7.4) database. “Size” represents the number of genes in each data set, “NES” the normalized enrichment score calculated by the GSEA, and the “FDR q-val” is error adjusted false discover rate. CREB-related transcription binding motifs were dominated. f GSEA plot indicates that genes down-regulated by fusion knockdown were over-represented at the right of the entire ranked list, which represent the down-regulated genes caused by CREB knockdown (NES −2.548 and FDR q-value < 0.0001). The solid bars represent each individual gene in fusion down-regulated gene set. g GSEA plot indicates that CREB down-regulated genes were over-represented at the right (down-regulated by Fusion KD) of the entire ranked list (NES −2.307 and FDR q-value < 0.0001). The solid bars represent each individual gene in fusion down-regulated gene set