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Volume 271, Number 37,
Issue of September 13, 1996
pp. 22499-22505
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
Role of Proximal Promoter Elements in Regulation of Renin
Gene Transcription
(Received for publication, April 10, 1996, and in revised form, June 21, 1996)
Nenad
Petrovic
,
Thomas A.
Black
,
John R.
Fabian
,
Colleen
Kane
,
Craig A.
Jones
,
John A.
Loudon
,
J. Pablo
Abonia
,
Curt D.
Sigmund
and
Kenneth W.
Gross
From the Department of Molecular and Cellular Biology, Roswell Park
Cancer Institute, Buffalo, New York 14263 and the
Cardiovascular Diseases Division, Departments of Internal
Medicine and Physiology and Biophysics, University of Iowa College of
Medicine, Iowa City, Iowa 52242
Mouse As4.1 cells, obtained after
transgene-targeted oncogenesis to induce neoplasia in renal
renin-expressing cells, express high levels of renin mRNA from the
endogenous Ren-1c gene. We have used these cells to
characterize the role of the Ren-1c proximal
promoter (+6 to 117) in the regulation of renin gene transcription.
It was found that 4.1 kilobases (kb) of Ren-1c
5 -flanking sequence, in combination with the proximal promoter, are
required for strong activation (~2 orders of magnitude over the basal
level of the promoter alone) of the chloramphenicol acetyltransferase
reporter in transfection assays. Within the 4.1-kb fragment, a 241-base
pair region was identified that retains full activity in an
orientation-independent manner in combination with the promoter. The
resulting transcripts initiate at the normal renin start site.
Electrophoretic mobility shift assays identified a sequence at
approximately position 60 in the promoter region that binds nuclear
proteins specific for renin-expressing As4.1 cells. Mutations in this
sequence, which disrupt binding of nuclear protein(s), completely
abolish activation of transcription by the 4.1-kb fragment. Activation
of transcription by the 241-base pair enhancer was still observed,
although it was diminished in magnitude (60-fold over the mutated
promoter alone). We present a model derived from the current data that
suggests that regulation of renin expression is achieved through
cooperation of transcription factors binding at the proximal promoter
element and a distal enhancer element to abrogate or override the
effects of an intervening negative regulatory region.

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[Full Text]
[PDF]
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[Abstract]
[Full Text]
[PDF]
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[Abstract]
[Full Text]
[PDF]
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[Abstract]
[Full Text]
[PDF]
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Y. Yan, C. A. Jones, C. D. Sigmund, K. W. Gross, and D. F. Catanzaro
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October 19, 1997;
81(4):
558 - 566.
[Abstract]
[Full Text]
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Downregulation of Renin Gene Expression by Interleukin-1
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August 1, 1997;
30(2):
230 - 235.
[Abstract]
[Full Text]
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K. Tamura, S. Umemura, N. Nyui, S. Yamaguchi, T. Ishigami, K. Hibi, M. Yabana, M. Kihara, A. Fukamizu, K. Murakami, et al.
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J. Biol. Chem.,
July 4, 1997;
272(27):
16845 - 16851.
[Abstract]
[Full Text]
[PDF]
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H. Baumann, Y. Wang, C. D. Richards, C. A. Jones, T. A. Black, and K. W. Gross
Endotoxin-induced Renal Inflammatory Response. ONCOSTATIN M AS A MAJOR MEDIATOR OF SUPPRESSED RENIN EXPRESSION
J. Biol. Chem.,
July 14, 2000;
275(29):
22014 - 22019.
[Abstract]
[Full Text]
[PDF]
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Q. Shi, K. W. Gross, and C. D. Sigmund
Retinoic Acid-mediated Activation of the Mouse Renin Enhancer
J. Biol. Chem.,
January 26, 2001;
276(5):
3597 - 3603.
[Abstract]
[Full Text]
[PDF]
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L. Pan, Y. Xie, T. A. Black, C. A. Jones, S. C. Pruitt, and K. W. Gross
An Abd-B Class HOX{middle dot}PBX Recognition Sequence Is Required for Expression from the Mouse Ren-1c Gene
J. Biol. Chem.,
August 24, 2001;
276(35):
32489 - 32494.
[Abstract]
[Full Text]
[PDF]
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Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.
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