Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells.
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.
Tian
H
H
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235, USA.
McKnight
S L
SL
Russell
D W
DW
D000595:Amino Acid Sequence; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D015152:Blotting, Northern; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry; D019281:Dimerization; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry; D012313:RNA / Q000032:analysis; D018336:Receptors, Aryl Hydrocarbon; D016415:Sequence Alignment; D017421:Sequence Analysis; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection / Q000235:genetics
C497396:ARNT protein, human; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D012313:RNA