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

Research output: Contribution to journalArticle

947 Scopus citations

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-1α) and lesser similarity with other members of the basic helix-loop-helix/PAS domain family of transcription factors. Like HIF-1α, 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-1α 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.

Original languageEnglish (US)
Pages (from-to)72-82
Number of pages11
JournalGenes and Development
Volume11
Issue number1
DOIs
StatePublished - Jan 1 1997

Keywords

  • PAS domain proteins
  • Tie-2
  • chromosome 2p16-21
  • endothelial cell transcription
  • hypoxia inducible factor
  • receptor tyrosine kinase

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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