Fig. 3

Transcription factor interaction networks within enhancer regions shift during AEC differentiation. A) Diagram of AEC enhancer regions selected for further study. Regions centered around the top 100 significantly enriched motifs within each cell type, dubbed “Interrogated Motifs”, colored red. 50 bp regions adjacent to the Interrogated Motif were subset (blue regions) to identify “Associated Motifs” that were significantly associated with the Interrogated Motifs. B-D) Unsupervised hierarchical clustering in AT2 cells (B) D4 AT-transitional cells (C), and AT1-like cells (D) of top 100 Interrogated Motifs (columns) and predicted Associated Motif significant interactions (rows). All HOMER TFBS were included in the analysis. Within the heatmaps, red indicates binding sequence similarity to the Interrogated Motif (positive control), blue indicates Associated Motifs had distinct core binding sequences, white indicates motif enrichment was not statistically significant. Families of TFs with similar core binding sequences were labeled with a distinct color to visually discern motif association patterns (column and row colors labels). E-G) Network analysis of AT2 (E), AT-transitional (F) and AT1-like (G) enhancer TF interactions. Each circle represents a “node”, or specific TF. Families of TFs are similarly colored according to the central key within the figure. Significant association is denoted by connecting ‘edges’, ie., lines (AT2: p < e-50; AT1-like: p < e-100). Length of edge/line is not indicative of significance level, all associations above the indicated thresholds are shown