Fig. 2: Identification and characterization of candidate enhancers at the BCE core locus. | Nature Communications

Fig. 2: Identification and characterization of candidate enhancers at the BCE core locus.

From: Auricular malformations are driven by copy number variations in a hierarchical enhancer cluster and a dominant enhancer recapitulates human pathogenesis

Fig. 2: Identification and characterization of candidate enhancers at the BCE core locus.

a Epigenomic profiling pinpoints enhancer elements at the BCE core locus. Integrated epigenomic analysis of the BCE core locus, combining in vivo data from human embryo craniofacial tissue at stages CS13-CS17 (including ear progenitor regions, upper part)27 with in vitro data from hESCs-derived human Cranial Neural Crest Cells (hCNCCs, lower part)31. CNV region shared across seven pedigrees is outlined by the golden rectangle. The chromatin state is represented through color coding (gray, Repressed PolyComb; purple, Bivalent Promoter; light yellow, Weak Enhancer; dark yellow, Active Enhancer; green, Weak Transcription; red, Promoter Upstream TSS), as defined on the Cotney lab craniofacial epigenome website (https://cotney.research.uchc.edu/craniofacial/). The epigenetic marks H3K4me3, H3K27me3, H3K27ac, and the presence of the transcriptional coactivator p300, in addition to H3K4me1 and CTCF signals in hCNCCs, are displayed. Candidate enhancers EC1, EC2, and EC3 are identified based on both datasets and are indicated by black rectangles. Previously reported mouse 594 bp ECR region resides in the mEC1 homologous sequence. b Differential chromatin interactions link CE enhancers to HMX1 promoter. Promoter Capture Hi-C (PC-HiC) analysis demonstrates the differential physical interactions between the CE locus and the HMX1 promoter in hESCs compared to late hCNCCs. For each cell line, the upper panel shows interaction profile (Gray full and dashed lines show expected counts and the upper bound of the 95% confidence intervals, respectively; Significant interactions with score ≥5 are shown in red, and sub-threshold interactions with 3 ≤ score < 5 are shown in blue); The middle panel shows called loops and the line color denotes the interaction strength; The bottom panel shows ATAC-seq track. The TAD boundary identified in Fig. 1c is depicted. ATAC-seq data and PC-HiC data for hESCs are sourced from GSE14532728 and GSE8682185, respectively.

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