Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

Harlan Barker; Seppo Parkkila

To investigate the transcriptional regulation of ACE2 gene we made predictions for the binding sites of transcription factors within the proximal promoter region of the intestine-specific and lungspecific human ACE2 transcript promoters. Our findings introduced several putative binding sites in the ACE2 promoter for known transcription factors, which showed high levels of coexpression with ACE2 in several tissues including the ileum, colon, and kidney. The identified transcription factors . CC-BY 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.13.038752 doi: bioRxiv preprint could represent potential candidate target molecules which regulate ACE2 expression. Two of our predictions, for HNF1A and HNF1B have been previously identified experimentally to drive ACE2 expression in pancreatic islet cells and insulinoma cells, respectively (36). Later work by the same group has shown that our prediction of FOXA binding sites in the ACE2 promoter are also likely correct (54) . It is of interest that ACE2 might be regulated by oxygen status. Zhang and coworkers previously demonstrated that ACE2 mRNA and protein levels increased during the early stages of hypoxia and decreased to near-baseline levels at later stages after hypoxia inducible factor (HIF)-1α accumulation (55) . Based on these findings ACE2 has been listed as a HIF1α-target gene (56), although it does not follow the typical HIF1α regulated expression pattern, nor is there any predicted HIF1α binding site in our analyses.