Fig. 2: ACE2 and TMPRSS2 regulatory elements and tissue-invariant topologically-associated domains.

a Human tissue DNase-seq signals for ACE2 [left] and TMPRSS2 [right] loci. Tissue-specific regulatory elements (red bar) and shared regulatory elements (black bar) are highlighted. Datasets were obtained from the Encyclopedia of DNA Elements (ENCODE) 2018 data release for Hg38⁴⁹ and visualized via the UCSC genome browser. Normalized signal replicate pools are depicted for each tissue type. ENCODE experimental designations are ENCSR747YZZ (small intestine), ENCSR619JTC (lung), ENCSR955NXV (kidney), ENCSR871OSL (left ventricle) and ENCSR341MVE (brain). b Schematic representation of topologically-associated domains (TADs) showing boundaries for regulatory elements that control expression of the genes within a TAD. The formation of a TAD is dependent on insulator elements bound by CCCTC-binding factor (CTCF). Enhancer association with promoters via long-range interactions may act to regulate expression. Some enhancers harbor SNPs that might alter the expression pattern of genes within a TAD. c Hi-C data for human tissues depict chromosome conformation into TADs around ACE2 (left) and TMPRSS2 (right). The locations of the respective genes are indicated in black. Lung, right ventricle, small bowel, and cortex datasets were obtained from Schmitt et al.⁹⁴. Aorta data were obtained from Leung et al.¹⁰⁸. Hi-C datasets were visualized in HiGlass¹⁰⁹ at 20-kb resolution. Datasets are aligned to human genome build Hg38. d Hi-C data for human lung fibroblast (IMR-90) and human endothelial (HUVEC) cell lines show higher-order chromosome organization as TADs. The genome locations of ACE2 (left) and TMPRSS2 (right) are indicated in black. Datasets aligned to human genome build Hg18 were obtained from Rao et al.⁹⁵ and visualized in HiGlass¹⁰⁹ at 8-kb resolution.