biostudies-literatureUnknown25(7)Richard DThe 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 as <i>SARS-CoV</i> and <i>SARS-CoV-2</i>. Improved characterization of <i>ACE2</i> regulation 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 on <i>ACE2</i> gene regulation in two different physiological contexts, identifying putative regulatory elements of <i>ACE2</i> expression. We perform functional validation of our computational predictions via targeted CRISPR-Cas9 deletions of these elements <i>in vitro</i>, finding them responsive to immune signaling and oxidative-stress pathways. This contributes to our understanding of <i>ACE2</i> gene 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 as <i>SARS-CoV-2</i>.iScience104614https://www.ebi.ac.uk/biostudies/studies/S-EPMC9213013biostudies-literatureIntronic regulation of SARS-CoV-2 receptor (ACE2) expression mediated by immune signaling and oxidative stress pathways.PMC9213013Hirota JMuthuirulan PMossman KCapellini TDDoxey ACBanerjee ARichard DAguiar JfalseIntronic regulation of SARS-CoV-2 receptor (ACE2) expression mediated by immune signaling and oxidative stress pathways.The 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 as <i>SARS-CoV</i> and <i>SARS-CoV-2</i>. Improved characterization of <i>ACE2</i> regulation 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 on <i>ACE2</i> gene regulation in two different physiological contexts, identifying putative regulatory elements of <i>ACE2</i> expression. We perform functional validation of our computational predictions via targeted CRISPR-Cas9 deletions of these elements <i>in vitro</i>, finding them responsive to immune signaling and oxidative-stress pathways. This contributes to our understanding of <i>ACE2</i> gene 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 as <i>SARS-CoV-2</i>.2022-01-01T00:00:00Z2022 Jul2024-10-18T18:38:20.349Z2022-07-10T02:22:24.829ZS-EPMC92130133575689310.1016/j.isci.2022.104614