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Background
HIF-2 alpha is also designated EPAS1 whose gene is mapped to 2p21-p16. The predicted mouse protein is 88% identical to human EPAS1. The human EPAS1 gene contains 15 exons and spans at least 120 kb. The positions of the introns within the genomic region encoding the N-terminal bHLH-PAS domains of EPAS1 and AHR are similar, suggesting that the 5-prime ends of the 2 genes may have arisen from a gene duplication event. Moreover, the predicted protein shares 48% sequence identity with HIF1-alpha, a bHLH-PAS transcription factor that induces EPO gene expression in cultured cells in response to hypoxia. Like HIF1A, EPAS1 binds to and activates transcription from the HIF1A response element derived from the 3-prime flanking region of the EPO gene. EPAS1 is predominantly expressed in highly vascularized tissues of adult humans and in endothelial cells of the mouse adult and embryo. Furthermore, EPAS1 may represent an important regulator of vascularization, perhaps involving the regulation of endothelial cell gene expression in response to hypoxia. HIF2A is expressed at relatively higher levels in villus sections of placenta and in lung samples compared with other tissues examined. In addition, The variation in EPAS1 influences the relative contribution of aerobic and anaerobic metabolism and hence the maximum sustainable metabolic power for a given event duration.