Fig. 3: The interaction landscape of the severe COVID-19 risk locus.

a, DpnII Capture-C-derived mean interaction count (n = 3 for all except CD14⁺, n = 2) and 1 s.d. (shading) for gene promoters in HUVECs, resting and activated T cells (CD4⁺ nonactivated/activated), monocytes (CD14⁺), CD71⁺ CD235⁺ erythroid cells and H1-hESCs. The enhancer containing rs17713054 is highlighted by a gray box. ATAC-seq/DNase I for each cell type is shown underneath in black. The CTCF track shows binding of the CCAAT-binding factor that acts as a boundary with forward and reverse motif orientation shown with arrowheads (red and blue, respectively). Three broad regulatory domains were identified as regions with overlapping interactions (region: chr3:45,400,000–46,200,000, hg38). Per-fragment interactions were smoothed using 400-bp bins and an 8-kb window. b, The rs17713054 regulatory ___domain in endothelial cells (HUVECs). Overlaid DNase I shows accessible sites in 95 cell types and H3K27ac shows active elements (region: chr3:45,730,000–45,930,000, hg38). Per-fragment interactions were smoothed using 250-bp bins and a 5-kb window. The solid line shows the mean interaction count (n = 3 independent samples) with 1 s.d. (shading). c, MCC of the rs17713054 enhancer in endothelial (HUVECs, blue) and erythroid (HUDEP-2, red) cells with tissue-specific open chromatin tracks (n = 3). Peak analysis of MCC using LanceOtron to compare the HUVEC and HUDEP-2 profiles identified two significantly enriched peaks in HUVEC cells (black triangles, P ≤ 1 × 10⁻⁹⁹⁹) that correspond to the LZTFL1 promoter and upstream CTCF site.