Regulation of theACE2locus in human airways cells

The angiotensin-converting enzyme 2 (ACE2) receptor is the gateway for SARS-CoV-2 to airway epithelium^1,2and the strong inflammatory response after viral infection is a hallmark in COVID-19 patients. Deciphering the regulation of the ACE2 gene is paramount for understanding the cell tropism of SARS-CoV-2 infection. Here we identify candidate regulatory elements in theACE2locus in human primary airway cells and lung tissue. Activating histone and promoter marks and Pol II loading characterize the intronicdACE2and define novel candidate enhancers distal to the genuineACE2promoter and within additional introns.dACE2, and to a lesser extentACE2, RNA levels increased in primary bronchial cells treated with interferons and this induction was mitigated by Janus kinase (JAK) inhibitors that are used therapeutically in COVID-19 patients. Our analyses provide insight into regulatory elements governing theACE2locus and highlight that JAK inhibitors are suitable tools to suppress interferon-activated genetic programs in bronchial cells.