Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells.

TLDR

EPAS1 shares ~48% identity with HIF‑1α and may regulate vascularization by responding to hypoxia in endothelial cells. The authors cloned and characterized EPAS1, a PAS domain transcription factor expressed in endothelial cells. They cloned EPAS1 and examined its DNA‑binding to the erythropoietin element, hypoxia‑stimulated activation, heterodimerization with the aryl hydrocarbon nuclear transporter, and endothelial‑restricted expression. EPAS1 binds the erythropoietin gene element, is activated by hypoxia, forms a heterodimer with the aryl hydrocarbon nuclear transporter, is expressed only in endothelial cells of mouse embryos, and specifically activates Tie‑2 transcription.

Abstract

Here we describe the cloning and characterization of a PAS domain transcription factor termed endothelial PAS-1 (EPAS1). This protein shares 48% sequence identity with hypoxia inducible factor (HIF-1alpha) and lesser similarity with other members of the basic helix-loop-helix/PAS domain family of transcription factors. Like HIF-1alpha, EPAS1 binds to and activates transcription from a DNA element originally isolated from the erythropoietin gene and containing the sequence 5'-GCCCTACGTGCTGTCTCA-3'. Activation by both HIF-1alpha and EPAS1 is stimulated by hypoxic conditions. EPAS1 forms a heterodimeric complex with the aryl hydrocarbon nuclear transporter prior to transcriptional activation of target genes. EPAS1 expression is limited to the endothelium of mouse embryos and, in agreement with its cell type-specific expression pattern, is capable of specifically activating the transcription of the endothelial tyrosine kinase gene Tie-2. These observations raise the possibility that EPAS1 may represent an important regulator of vascularization, perhaps involving the regulation of endothelial cell gene expression in response to hypoxia.