Figure 2.

Genome-wide identification of HNF4A and GATA6 binding sites. (A) Genomic distribution of HNF4A and GATA6 ChIP-seq regions compared to genomic average. Promoter is defined as −2.5 to +0.5 kb relative to the TSS. (B) The top three motifs from de novo motif discovery and their associated transcription factor found in ChIP-seq regions for HNF4A (top) and GATA6 (bottom). The frequency of motif occurrence is shown, and motifs are sorted by P-value. (C) Venn diagram of overlapping binding regions from HNF4A and GATA6 ChIP-seq. P-value was calculated using Fisher's exact test. (D) Heatmap and tag density plots of ChIP-seq signals for HNF4A and GATA6 at regions bound by HNF4A only, GATA6 only, or both HNF4A and GATA6. The ATAC-seq signals at the same regions in Het1A and OE19 cells are shown. (E) UCSC Genome Browser tracks showing ChIP-seq tracks at three loci (IRAK2, CLDN18, and HES4). GATA6 and/or HNF4A bound regions are boxed. (F) Tag density plots of ATAC-seq signal at regions bound by HNF4A only, GATA6 only, or both HNF4A and GATA6 in normal and EAC tumor tissue. (G) Footprinting of ATAC-seq data from normal and EAC tissue (bottom) on 150-bp regions surrounding the HNF4A or GATA6 transcription factor motifs found in HNF4A + GATA6 co-occupied ChIP-seq regions. (H) Distribution of ATAC-seq footprints in “open in cancer” regions that coincide with ChIP-seq regions of HNF4A and GATA6.