Figure 4.

Barrett's esophagus ATAC-seq is related to EAC. (A) PCA plot of the normalized ATAC-seq signal across the top 50,000 regions of all three normal (blue), four Barrett's (black), and four EAC (red) tissue samples. (B) Heatmap of normalized Tn5 cleavage events in a ±250-bp region surrounding the summit of differentially accessible nonpromoter and promoter regions (greater than fivefold change, Q < 0.05) in normal versus Barrett's samples. (C) Pie charts representing the proportion of differentially accessible regions that are located in promoter and nonpromoter regions (top) and regions that are fivefold more open or closed in Barrett's tissue (bottom). (D) Top five DNA motifs derived from de novo motif discovery and their associated transcription factor that are enriched in “open in Barrett's” (top) or “closed in Barrett's” (bottom) nonpromoter regions. The frequency of motif occurrence is shown, and the motifs are sorted by P-value. (E) Scatter bag plot of differential chromatin accessibility (x-axis) and footprinting (y-axis) depth around human transcription factor binding motifs in normal and Barrett's tissue. Significant outliers (P < 0.05) are represented in red. Motifs with enrichment in “open in Barrett's” and “closed in Barrett's” regions are labeled. (F) Plot of Log₂(1 + FPKM) values of transcription factors with enriched motifs in differentially accessible regions from normal (blue) versus Barrett's analysis (“open in Barrett's”) in RNA-seq data from normal or Barrett's (black). Mean is represented by a black bar with standard deviation shown above and below. (****) P < 0.0001; (***) P < 0.001. (G) Heatmap of ATAC-seq signal from normal, Barrett's, and EAC tissue at differentially “open in Barrett's,” “closed in Barrett's,” and a control set of 500 random nonsignificant differential accessible regions. (H) UCSC Genome Browsers tracks of ATAC-seq signal at two example loci (LGALS4 and TFAP2B) with differentially accessible regions boxed. (I) Expression of LGALS4 and TFAP2B in normal, Barrett's, and EAC tissue (Maag et al. 2017). Mean is represented by a black bar with standard deviation shown above and below. (****) P < 0.0001; (***) P < 0.001.