Motif enrichment analysis reveals candidate TFs acting via endoderm HCNE CRMs. (A,B) High-confidence de novo motifs enriched in HCNEs overlapping both human PFG H3K27ac peaks and sox17E > sox17M DARs at 28 and/or 48 hpf for the human (A) and zebrafish (B) HCNE sequences. P-values and closest match vertebrate TFs assigned by HOMER are indicated. (C) Hierarchical clustering of enrichment of known motifs in human and zebrafish endoderm HCNEs overlapping both sox17E > sox17M DARs at 28 and/or 48 hpf, as well as human AFG, PFG, and MHG H3K27ac peaks as indicated. Enrichment in both human and zebrafish HCNE sequences is shown. RNA-seq expression of TF genes corresponding to enriched motifs is indicated as fragments Per Kilobase of transcript per Million mapped reads (FPKM) for both human and zebrafish data sets as indicated. (AFG) Anterior foregut; (PFG) posterior foregut; (MHG) mid/hindgut; (PP) pancreatic progenitors. Zebrafish have multiple orthologs of mammalian TF genes owing to the additional whole genome and other small duplications during teleost evolution. Where present, a, b, and c paralogs are depicted. (*) Although the enriched motif is FOXA2:EBOX FPKM, heatmap indicates FOXA2 expression alone.