Abstract
Endothelial PAS domain-containing protein 1 (EPAS1), also HIF2α, 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 HIF1α. 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.
Highlights
Endothelial PAS domain-containing protein 1 (EPAS1), known as Hypoxiainducible factor 2 alpha (HIF2α), is an alpha subunit of heterodimeric transcription complex hypoxia-inducible transcription factor (HIF)-2
In the genome browsers Ensembl and National Centre for Biotechnology Information (NCBI), EPAS1 is indicated with the ID numbers ENSG00000116016 and 2034, respectively [16,17]
The EPAS1 gene is expressed in various types of tissues, with enhanced expression in the lungs (Figure 3)
Summary
Endothelial PAS domain-containing protein 1 (EPAS1), known as Hypoxiainducible factor 2 alpha (HIF2α), is an alpha subunit of heterodimeric transcription complex HIF-2. Transcription complexes HIFs function as master regulators of oxygen homeostasis [1]. HIFs regulate numerous responses to hypoxia through transcription activation of multiple genes that either increase oxygen delivery or decrease oxygen consumption. The former group includes gene for erythropoietin (EPO), which regulates red blood cell production and gene for vascular endothelial growth factor (VEGF), which promotes angiogenesis and increases vascular permeability and local tissue oxygenation. HIFs regulate genes involved in iron metabolism and bone marrow microenvironment adjustments, which facilitate erythroid progenitor proliferation and maturation. Due to hypoxic environment in early developmental stages of embryos, HIFs are involved in the mammalian embryogenesis [3]
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