摘要：SummaryThe angiotensin-converting enzyme 2 (ACE2) protein is a key catalytic regulator of the renin-angiotensin system (RAS), involved in fluid homeostasis and blood pressure modulation. ACE2 also serves as a cell-surface receptor for some coronaviruses such asSARS-CoVandSARS-CoV-2. Improved characterization ofACE2regulation may help us understand the effects of pre-existing conditions on COVID-19 incidence, as well as pathogenic dysregulation following viral infection. Here, we perform bioinformatic analyses to hypothesize onACE2gene regulation in two different physiological contexts, identifying putative regulatory elements ofACE2expression. We perform functional validation of our computational predictions via targeted CRISPR-Cas9 deletions of these elementsin vitro, finding them responsive to immune signaling and oxidative-stress pathways. This contributes to our understanding ofACE2gene regulation at baseline and immune challenge. Our work supports pursuit of these putative mechanisms in our understanding of infection/disease caused by current, and future, SARS-related viruses such asSARS-CoV-2.Graphical abstractDisplay OmittedHighlights•Lung expression patterns suggestACE2regulation by immune and oxidative signaling•CRISPR deletion of intronic regulatory elements (REs) altersACE2expression•Effects of RE deletion are modified by immune stimulation and oxidative stress•Propose two mechanisms for regulatingACE2at baseline and after immune challengeBiological sciences; Molecular biology; Immunology; Virology
