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Originally published In Press as doi:10.1074/jbc.M011344200 on January 22, 2001
J. Biol. Chem., Vol. 276, Issue 16, 12645-12653, April 20, 2001
Molecular Regulation of the Endothelin-1 Gene by
Hypoxia
CONTRIBUTIONS OF HYPOXIA-INDUCIBLE FACTOR-1, ACTIVATOR
PROTEIN-1, GATA-2, AND p300/CBP*
Kazuhito
Yamashita,
Daryl J.
Discher,
Jing
Hu,
Nanette H.
Bishopric, and
Keith A.
Webster
From the Department of Molecular and Cellular Pharmacology,
University of Miami Medical Center, Miami, Florida 33149
Endothelin-1 (ET-1) is a peptide hormone
with potent vasoconstrictor properties which is synthesized and
secreted predominantly by vascular endothelial cells. Its production is
regulated by numerous stimuli including ischemia and hypoxia, and the
enhanced levels that occur during myocardial ischemia may contribute to the progression of heart failure. We reported previously a preliminary characterization of a hypoxia-inducible factor-1 (HIF-1) binding site
in the human ET-1 promoter which contributed to the activation of ET-1
expression in endothelial cells. We report here that the HIF-1 binding
site alone is not sufficient for the response to hypoxia but requires
an additional 50 base pairs of flanking sequence that includes binding
sites for the factors activator protein-1 (AP-1), GATA-2, and
CAAT-binding factor (NF-1). Mutation of any one of these sites or the
HIF-1 site eliminated induction by hypoxia. Mutations of the AP-1 and
GATA-2 sites, but not the HIF-1 site, were complemented by
overexpressing AP-1, GATA-2, HIF-1 , or the activator protein
p300/CBP, restoring the response to hypoxia. Binding studies in
vitro confirmed physical associations among GATA-2, AP-1, and
HIF-1 factors. Overexpression or depletion of p300/CBP modulated the
level of ET-1 promoter expression as well as the endogenous ET-1
transcript but did not change the fold induction by hypoxia in either
case. Regulation of the ET-1 promoter by hypoxia in
non-endothelial cells required overexpression of GATA-2 and HIF-1 .
The results support essential roles for AP-1, GATA-2, and NF-1 in
stabilizing the binding of HIF-1 and promoting recruitment of p300/CBP
to the ET-1 hypoxia response complex.
*
This work was supported by Grant HL44578 from the National
Institutes of Health (to K. A. W.) and by a postdoctoral fellowship from the American Heart Association, Florida Affiliate (to K. Y.). A
preliminary report of this work has been published in abstract form
(Yamashita, K., Discher, D. J., Hu, J., Bishopric, N. H., and
Webster, K. A. (1999) Circulation 98, 74).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Molecular and
Cellular Pharmacology, Rosenstiel Medical Science Bldg., Rm. 6038, University of Miami Medical Center, 1600 NW 10th Ave., Miami, FL
33136. Tel.: 305-243-6779; Fax: 305-243-3082; E-mail: kwebster@chroma.med.miami.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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[Full Text]
[PDF]
|
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[Abstract]
[Full Text]
[PDF]
|
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|
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|
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[Full Text]
[PDF]
|
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|
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|
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Hypoxia-induced pulmonary endothelin-1 expression is unaltered by nitric oxide
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92(3):
1152 - 1158.
[Abstract]
[Full Text]
[PDF]
|
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|

|
 |

|
 |
 
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c-Jun and Hypoxia-Inducible Factor 1 Functionally Cooperate in Hypoxia-Induced Gene Transcription
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22(1):
12 - 22.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Vezf1/DB1 Is an Endothelial Cell-specific Transcription Factor That Regulates Expression of the Endothelin-1 Promoter
J. Biol. Chem.,
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276(42):
39197 - 39205.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. D. Kline, Y.-J. Peng, D. J. Manalo, G. L. Semenza, and N. R. Prabhakar
Defective carotid body function and impaired ventilatory responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alpha
PNAS,
January 22, 2002;
99(2):
821 - 826.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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