Fig. 3

Identification of super-enhancers in 501mel cells and analysis of super-enhancer-associated gene response to MEK inhibition. a Distribution of H3K27ac ChIP-Seq signal at enhancers (input-subtracted reads per million per enhancer region) in 501mel cells under DMSO treatment. Enhancers are ranked by decreasing H3K27ac ChIP-Seq signal; the gray dashed line demarcates the boundary between super-enhancers (red) and typical enhancers (gray). The transcription factors listed exhibit 3 notable characteristics: each of their genomic loci are associated with nearby super-enhancers (indicated by black lines), each show differential mRNA expression under AZD6244 treatment (shown in Additional file 2: Table S1), and each also have enriched motifs when all super-enhancer regions are examined (shown in b). Therefore, these transcription factors are not only associated with a neighboring super-enhancer, but themselves have the capacity to bind other super-enhancers throughout the genome, raising the possibility of autoregulatory loops involving these key factors. Of note, MITF is shown twice because the MITF genomic locus has two independent super-enhancers. b The top five transcription factor binding motifs significantly enriched in 501mel super-enhancers; the fraction of super-enhancer regions containing the indicated motifs and the p values for the overrepresentation of each motif are shown. c Venn diagram showing the overlap between all genes associated with super-enhancers and genes whose expression is significantly altered by AZD6244 in 501mel cells. GO analysis was performed using the PANTHER overrepresentation test, to identify top biological pathways enriched for upregulated (upper panel, red) and downregulated (lower panel, green) genes with super-enhancer signatures in 501mel cells. p values represent FDR-adjusted (Bonferroni method) significance of enrichment for pathway members. d Venn diagram showing the overlap of super-enhancers in control (DMSO-treated) and AZD6244-treated 501mel cells