General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia

G L Wang, G L Semenza, G L Wang, G L Semenza

Abstract

Transcription of the human erythropoietin (EPO) gene is activated in Hep3B cells exposed to hypoxia. Hypoxia-inducible factor 1 (HIF-1) is a nuclear factor whose DNA binding activity is induced by hypoxia in Hep3B cells, and HIF-1 binds at a site in the EPO gene enhancer that is required for hypoxic activation of transcription. In this paper, we demonstrate that HIF-1 DNA binding activity is also induced by hypoxia in a variety of mammalian cell lines in which the EPO gene is not transcribed. The composition of the HIF-1 DNA binding complex and its isolated DNA binding subunit and the mechanism of HIF-1 activation appear to be similar or identical in EPO-producing and non-EPO-producing cells. Transcription of reporter genes containing the EPO gene enhancer is induced by hypoxia in non-EPO-producing cells and mutations that eliminate HIF-1 binding eliminate inducibility. These results provide evidence that HIF-1 and its recognition sequence are common components of a general mammalian cellular response to hypoxia.

References

    1. Nature. 1970 Aug 15;227(5259):680-5
    1. J Clin Invest. 1990 Aug;86(2):670-4
    1. Cell. 1988 Aug 26;54(5):671-83
    1. Science. 1988 Dec 9;242(4884):1412-5
    1. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2301-5
    1. Mol Cell Biol. 1990 Mar;10(3):930-8
    1. J Biol Chem. 1990 Aug 25;265(24):14100-4
    1. Blood. 1991 Jan 15;77(2):271-7
    1. Blood. 1991 Feb 1;77(3):419-34
    1. Nature. 1991 Mar 14;350(6314):170-2
    1. Blood. 1991 Jun 1;77(11):2497-503
    1. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5680-4
    1. J Biol Chem. 1991 Aug 25;266(24):15563-6
    1. J Clin Invest. 1991 Sep;88(3):1054-7
    1. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8725-9
    1. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10553-7
    1. Physiol Rev. 1992 Apr;72(2):449-89
    1. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4280-4
    1. Nature. 1992 Oct 29;359(6398):843-5
    1. Mol Cell Biol. 1992 Dec;12(12):5373-85
    1. Mol Cell Biol. 1992 Dec;12(12):5447-54
    1. J Clin Invest. 1992 Dec;90(6):2333-9
    1. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2423-7
    1. Mol Cell Biochem. 1987 Sep;77(1):19-28

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