Integration and Visualization of Regulatory Elements and Variations of the EPAS1 Gene in Human

Endothelial PAS domain-containing protein 1 (EPAS1), also HIF2 ff, is an alpha subunit of hypoxia-inducible transcription factor (HIF), which mediates cellular and systemic response to hypoxia. EPAS1 has an important role in the transcription of many hypoxia-responsive genes, however, it has been less researched than HIF1ff. The aim of this study was to integrate an increasing number of data on EPAS1 into a map of diverse OMICs elements. Publications, databases, and bioinformatics tools were examined, including Ensembl, MethPrimer, STRING, miRTarBase, COSMIC, and LOVD. The EPAS1 expression, stability, and activity are tightly regulated on several OMICs levels to maintain complex oxygen homeostasis. In the integrative EPAS1 map we included: 31 promoter-binding proteins, 13 interacting miRNAs and one lncRNA, and 16 post-translational modifications regulating EPAS1 protein abundance. EPAS1 has been associated with various cancer types and other diseases. The development of neuroendocrine tumors and erythrocytosis was shown to be associated with 11 somatic and 20 germline variants. The integrative map also includes 12 EPAS1 target genes and 27 interacting proteins. The study introduced the first integrative map of diverse genomics, transcriptomics, proteomics, regulomics, and interactomics data associated with EPAS1, to enable a better understanding of EPAS1 activity and regulation and support future research.

Automated summary

EPAS1, also known as HIF2 ff, plays a crucial role in mediating cellular and systemic response to hypoxia by regulating the transcription of many hypoxia-responsive genes. This study integrated a variety of data on EPAS1, including promoter-binding proteins, miRNAs, post-translational modifications, and disease-related variants and target genes, to enhance understanding of EPAS1 activity and regulation. The comprehensive map provides insights into the complex mechanisms that regulate EPAS1 expression, stability, and activity on various OMICs levels.