Fig. 2: 3D chromatin architecture across the Shox2 regulatory landscape in distinct tissues.
From: A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival
A C-HiC analysis of the genomic region containing the Shox2 TAD64 in wildtype mouse embryonic forelimb (FL), mandible (MD) and heart (HT) at E11.5 (see also Supplementary Fig. 2). The chr3:65977711-67631930 (mm10) interval is shown. Upper panels (for each tissue): Hi-C contact map revealing upstream (U-dom) and downstream (D-dom) domains flanking the Shox2 gene. Middle panels: Stronger (gray boxes, p < 0.01) and weaker (brown boxes, p > 0.01, <0.05) domain boundaries based on TAD separation score (Wilcoxon rank-sum test). A matrix showing normalized inter-domain insulation score (blue = weak insulation, red = strong insulation) is plotted below. Bottom panels: Virtual 4 C (v4C) using a Shox2-centered viewpoint shows Shox2 promoter interaction profiles in the different tissues. Shox2 contacting regions (q < 0.1, Supplementary Data 2) as determined by GOTHiC140 are shown on top. Red arrows point to chromatin domain anchors. Asterisk marks a high-density contact domain (HCD) observed only in heart tissue (chr3:66402500-66572500). Black arrow indicates reduction of internal D-dom contacts between elements inside the HCD and outside in the heart sample (see also Supplementary Fig. 2). B Top: CTCF enrichment in mESCs64 (gray) and newborn mouse hearts at P058 (orange). Bottom: CTCF motif orientation (red/blue) and strength (gradient). Protein coding genes (gene bodies) are indicated below. DEs, predicted gene desert enhancers validated in Fig. 1 (blue: tissue-specific activity). C C-HiC subtraction to visualize tissue-specific contacts for each tissue comparison (red/blue). Plots below display the corresponding subtracted inter-domain insulation scores. Dashed lines demarcate the HCD borders.
