Richard Daniel, Muthuirulan Pushpanathan, Aguiar Jennifer, Doxey Andrew C, Banerjee Arinjay, Mossman Karen, Hirota Jeremy, Capellini Terence D
Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
Department of Biology, University of Waterloo, Waterloo, ON N2L3G1, Canada.
iScience. 2022 Jul 15;25(7):104614. doi: 10.1016/j.isci.2022.104614. Epub 2022 Jun 15.
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 and . Improved characterization of 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 gene regulation in two different physiological contexts, identifying putative regulatory elements of expression. We perform functional validation of our computational predictions via targeted CRISPR-Cas9 deletions of these elements , finding them responsive to immune signaling and oxidative-stress pathways. This contributes to our understanding of 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 .
血管紧张素转换酶2（ACE2）蛋白是肾素-血管紧张素系统（RAS）的关键催化调节因子，参与体液平衡和血压调节。ACE2还是某些冠状病毒（如 和 ）的细胞表面受体。对 调节的进一步表征可能有助于我们了解既往疾病状况对COVID-19发病率的影响，以及病毒感染后致病性失调情况。在此，我们进行生物信息学分析，以推测 在两种不同生理背景下的基因调控情况，确定 表达的假定调控元件。我们通过对这些元件进行靶向CRISPR-Cas9缺失来对计算预测进行功能验证，发现它们对免疫信号和氧化应激途径有反应。这有助于我们理解 在基线和免疫挑战时的基因调控。我们的工作支持在理解由当前及未来与SARS相关的病毒（如 ）引起的感染/疾病过程中探索这些假定机制。
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