Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension

Guang L. Wang, Bing Hua Jiang, Elizabeth A. Rue, Gregg L. Semenza

Research output: Contribution to journalArticlepeer-review


Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. We show that both HIF-1 subunits are basic-helix-loop-helix proteins containing a PAS domain, defined by its presence in the Drosophila Per and Sim proteins and in the mammalian ARNT and AHR proteins. HIF-1α is most closely related to Sim. HIF-1β is a series of ARNT gene products, which can thus heterodimerize with either HIF-1α or AHR. HIF-1α and HIF-1β (ARNT) RNA and protein levels were induced in cells exposed to 1% O2 and decayed rapidly upon return of the cells to 20% O2, consistent with the role of HIF-1 as a mediator of transcriptional responses to hypoxia.

Original languageEnglish (US)
Pages (from-to)5510-5514
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - Jun 6 1995


  • dioxin receptor
  • erythropoietin
  • hypoxia
  • transcription

ASJC Scopus subject areas

  • General


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