Table 2 Regulation of ACE2 transcription
From: ACE2 in chronic disease and COVID-19: gene regulation and post-translational modification
Regulation of ACE2 transcription | ||
|---|---|---|
Name | Description | Ref. |
Upregulation | ||
 Ikaros | Ikaros binds to the ACE2 promoter at the − 525 to − 519 bp (5′-ATTTGGA-3′) region, enhancing ACE2 transcription | [30] |
 HNF1α/1β | HNF1α or HNF1β bind to the − 346 to − 330 (5′-GTATCTTTAACAGCTTT-3′), − 329 to − 312 (5′-CTAGGAAAATATTAACCA-3′), − 259 to − 242 (5′-AGGATTAAAGAATAACGT-3′), and − 921 to − 915 bp (5′-AGTCATA-3′) regions of the ACE2 promoter, inducing ACE2 transcription HNF1α and HNF1β are downregulated in human maturity-onset diabetes of the young (MODY) type 3 and MODY type 5 patients, respectively | |
 HNF4α | HNF4α binds to the − 7436 to − 7423 (5′-GTGATCTTTGACTC-3′) and − 5533 to − 5520 bp (5′-ATGTACTTTGCTCT-3′) regions of the ACE2 promoter HNF4α and ACE2 mRNA levels are decreased by cyclosporine | [35] |
 GATA6 | GATA6 binds to − 408 to − 403 (5′-TTATCT-3′) and − 351 to − 341 bp (5′-TCCGTGTATCT-3′) regions of the ACE2 promoter, inducing ACE2 transcription GATA6 mRNA levels are increased in the lung samples from COVID-19 patients | [36] |
 STAT3 | STAT3 binds to − 2031 to − 2021 bp (5′-TTCAACCTTTT-3′) region of the ACE2 promoter, enhancing ACE2 transcription Activated STAT3 is positively correlated with the protein levels of ACE2 in lung tissues of pulmonary chronic inflammation or lung cancer patients IL-6/STAT3 signaling stimulates ACE2 transcription in inflammatory diseases ACE2 mRNA levels are inhibited by the IL-6 inhibitor 6-O-angeloylplenolin | |
 SIRT1 | SIRT1 binds to − 15,794 to − 15,656, − 15,621 to − 15,521 and − 15,607 to − 15,505 bp regions of the ACE2 promoter, inducing ACE2 transcription | [49] |
 Histone 3 | Acetylated histone 3 binds to the ACE2 promoter, epigenetically enhancing ACE2 transcription | [52] |
 DYRK1A | DYRK1A increases ACE2 mRNA levels by promoting chromatin accessibility, leading to enhancement of SARS-CoV-2 infection | [62] |
 Interferon | IFN-α2, IFN-β, and IFN-γ induce ACE2 transcription through STAT1 in virus-infected airway epithelial cells IFN-α, IFN-β, IFN-γ, and IFN-λ1-3 increase truncated ACE2 mRNA isoform IFN levels are increased during viral infection | |
 SMAD4, EP300, PIAS1, BAMBI | Genome-wide CRISPR gene knockout screening analysis shows that SMAD4, EP300, PIAS1, or BAMBI positively regulates ACE2 mRNA levels | [70] |
Downregulation | ||
 Brg1-FoxM1 | Brg1-FoxM1 protein complex binds to the ACE2 promoter, leading to inhibition of the ACE2 transcription The upregulation of Brg1 is positively correlated with the disease development of human hypertrophic cardiomyopathy TCA-reduced ACE2 protein levels are recovered by the FoxM1 inhibitor thiostrepton | [71] |
 ERRα | ERRα binds to the ACE2 promoter, reducing ACE2 transcription | [74] |
 EZH2 | EZH2 induces lysine 27 trimethylation on histon 3 (H3K27me3) and blocks acetylated H3 (H3K27ac) binding to the ACE2 promoter, leading to downregulation of ACE2 gene expression | [77] |