Figure 6.

Scores of mean position weight matrix (PWM) of key cis-elements in the proximal promoters of ACE2 genes that containing binding sites for canonical IFN-dependent transcription factors, which include ISRE/STAT1/3, IRF1, IRF3/7 and IRF8, as well as C/EBP as a core transcription factors for pro-inflammatory response. These IFN-dependent transcription factors, particularly IRF3/7 and ISRE/STAT critical for IFN stimulation, are differentially enriched in the promoter regions of ACE2 genes in a species-dependent way. Especially, increased enrichment of ISRE/STAT1/3 and IRF3/7 binding sites are detected in the SARS-CoV2/COVID19 susceptible species (indicated with solid orange or red circles, respectively). In contrast, the PWM for IRF1 and C/EBP, which regulate inflammation, are less differentially enriched in ACE2 promoters from different animal species. The promoters of a typical human robust interferon-stimulated gene (ISG) 15 and IRF1 (a typical tunable ISG) are used as references. Higher enrichment of ISRE/STAT1/3 and IRF3/7 corresponds to SARS-CoV2 susceptibility in experimentally validated animal species and humans. Abbreviations: C/EBP, CCAAT/enhancer binding protein; IRF, interferon-regulatory factor; ISRE, Interferon-sensitive response element; STAT, Signal transducer and activator of transcription; PWM, position weight matrix. The PWM tools are used through https://ccg.epfl.ch/cgi-bin/pwmtools.