Fig. 3
Discovery and characterization of enhancer activity in IBD a. Conservation analysis of enhancer regions. X-axis shows the distance from the center of regions. Y-axis shows average PhyloP100 vertebrate conservation score65 for strict and permissive enhancer sets, non-transcribed DHSs from gut27 and random non-genic regions. P-values indicate Mann–Whitney U tests between conservation scores in the ±200 bp region (dashed lines). Number of regions in each set are shown (overlapping regions were discarded). b Transcription factor binding enrichment within CAGE-defined enhancer regions. Heat map rows correspond to the 10,670 enhancer predictions, sorted by distance between bidirectional CAGE peaks. X-axis corresponds to the ±2000 bp region centered on enhancer midpoints. CAGE peak summits are shown as black lines. Color intensity corresponds to number of ENCODE transcription factor ChIP-seq peaks (all ENCODE cells) overlapping a given region. c H3K27ac and H3K4me1 ChIP-seq enrichment within enhancer regions identified by CAGE in gut biopsies. Heat maps are constructed as in b, but show ChIP-seq signal from H3K27ac and H3K4me1 from rectal/colonic mucosa, T helper and CD14+ cells27. Colors are assigned based on observed min and max ChIP-seq intensity values within each heatmap. d Principal component analysis based on CAGE expression within enhancer regions. Plot is organized as Fig. 2a. e Number of differentially expressed enhancers. Bar plot shows the number of differentially expressed enhancers per group, organized as Fig. 2b. f Predicted transcription factor site enrichment in enhancer and TSS regions. Each row shows data related to one transcription factor. Left panel shows site enrichment P value in respective groups of differentially expressed enhancers or promoters for the sites corresponding to the relevant motif, as indicated by color scale. Middle panel shows the CAGE expression as log2 TPM for the transcription factor across groups as boxplots. Right panel shows motif sequence logo. g Linkage between enhancer and TSS through co-expression. Y-axis shows the fraction of CAGE TSSs that can be linked to enhancers within 500 kb through co-expression correlation, split by how many enhancers each TSS is linked to. X-axis shows sets of TSSs split by their differential expression as in Fig. 2b
