|
|
 Previous Article | Table of Contents | Next Article 
Mouse Hypoxia-Inducible Factor-1 Is Encoded by Two Different mRNA
Isoforms: Expression From a Tissue-Specific and a Housekeeping-Type
Promoter
Roland H. Wenger,
Andreas Rolfs,
Patrick Spielmann,
Dieter R. Zimmermann, and
Max Gassmann
From the Institute of Physiology, University of Zürich-Irchel,
Zürich; and the Department of Pathology, University of
Zürich, Zürich, Switzerland.
Hypoxic induction of erythropoietin (Epo) and other oxygen-dependent
genes is mediated by the hypoxia-inducible factor-1 (HIF-1), a
heterodimeric transactivator consisting of an  and a  subunit. We
previously found that the mouse gene encoding HIF-1 harbors two
alternative first exons (I.1 and I.2), giving rise to two different
HIF-1 mRNA isoforms. Here, we show by RNase
protection analysis that the exon I.1-derived mRNA isoform is
differentially expressed in mouse tissues, being highest in kidney,
tongue, stomach, and testis, but undetectable in liver, whereas the
exon I.2 mRNA isoform is ubiquitously expressed. Sequence and
methylation analysis showed that, in contrast to exon I.1, exon I.2
resides within a region showing typical features of a CpG island, known
to be associated with the 5 end of housekeeping genes. We
identified a 232-bp minimal exon I.2 promoter that strongly induced
reporter gene expression in mouse L929 fibroblasts and Hepa1 hepatoma
cells. In contrast to L929 cells, the exon I.1 promoter was inactive in
Hepa1 cells and hypoxic exposure (1% O2) markedly reduced
exon I.2 promoter activity in Hepa1 cells. Prolonged exposure of mice to hypoxia (7.5% O2 for up to 72 hours) also caused a
decrease in liver HIF-1 mRNA, whereas aldolase mRNA levels
increased. These findings might be related to the relatively low Epo
levels in the adult liver.
Blood, Vol. 91 No. 9 (May 1), 1998:
pp. 3471-3480
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. Schipani and T. L. Clemens
Hypoxia and the Hypoxia-Inducible Factors in the Skeleton
IBMS BoneKEy,
August 1, 2008;
5(8):
275 - 284.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Srinivasan, D. T. Bolick, D. Lukashev, C. Lappas, M. Sitkovsky, K. R. Lynch, and C. C. Hedrick
Sphingosine-1-Phosphate Reduces CD4+ T-Cell Activation in Type 1 Diabetes Through Regulation of Hypoxia-Inducible Factor Short Isoform I.1 and CD69
Diabetes,
February 1, 2008;
57(2):
484 - 493.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Borter, M. Niessen, R. Zuellig, G. A. Spinas, P. Spielmann, G. Camenisch, and R. H. Wenger
Glucose-Stimulated Insulin Production in Mice Deficient for the PAS Kinase PASKIN
Diabetes,
January 1, 2007;
56(1):
113 - 117.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ramanathan, G. Pinhal-Enfield, I. Hao, and S. J. Leibovich
Synergistic Up-Regulation of Vascular Endothelial Growth Factor (VEGF) Expression in Macrophages by Adenosine A2A Receptor Agonists and Endotoxin Involves Transcriptional Regulation via the Hypoxia Response Element in the VEGF Promoter
Mol. Biol. Cell,
January 1, 2007;
18(1):
14 - 23.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Lukashev, B. Klebanov, H. Kojima, A. Grinberg, A. Ohta, L. Berenfeld, R. H. Wenger, A. Ohta, and M. Sitkovsky
Cutting Edge: Hypoxia-Inducible Factor 1{alpha} and Its Activation-Inducible Short Isoform I.1 Negatively Regulate Functions of CD4+ and CD8+ T Lymphocytes
J. Immunol.,
October 15, 2006;
177(8):
4962 - 4965.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-J. Hu, S. Iyer, A. Sataur, K. L. Covello, L. A. Chodosh, and M. C. Simon
Differential Regulation of the Transcriptional Activities of Hypoxia-Inducible Factor 1 Alpha (HIF-1{alpha}) and HIF-2{alpha} in Stem Cells.
Mol. Cell. Biol.,
May 1, 2006;
26(9):
3514 - 3526.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Busca, E. Berra, C. Gaggioli, M. Khaled, K. Bille, B. Marchetti, R. Thyss, G. Fitsialos, L. Larribere, C. Bertolotto, et al.
Hypoxia-inducible factor 1{alpha} is a new target of microphthalmia-associated transcription factor (MITF) in melanoma cells
J. Cell Biol.,
July 4, 2005;
170(1):
49 - 59.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Krick, B. G. Eul, J. Hanze, R. Savai, F. Grimminger, W. Seeger, and F. Rose
Role of Hypoxia-Inducible Factor-1{alpha} in Hypoxia-Induced Apoptosis of Primary Alveolar Epithelial Type II Cells
Am. J. Respir. Cell Mol. Biol.,
May 1, 2005;
32(5):
395 - 403.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. V. Beischlag, R. T. Taylor, D. W. Rose, D. Yoon, Y. Chen, W.-H. Lee, M. G. Rosenfeld, and O. Hankinson
Recruitment of Thyroid Hormone Receptor/Retinoblastoma-interacting Protein 230 by the Aryl Hydrocarbon Receptor Nuclear Translocator Is Required for the Transcriptional Response to Both Dioxin and Hypoxia
J. Biol. Chem.,
December 24, 2004;
279(52):
54620 - 54628.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Fukasawa, T. Tsuchiya, E. Takayama, N. Shinomiya, K. Uyeda, R. Sakakibara, and S. Seki
Identification and Characterization of the Hypoxia-Responsive Element of the Human Placental 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase Gene
J. Biochem.,
September 1, 2004;
136(3):
273 - 277.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Depping, S. Hagele, K. F. Wagner, R. J. Wiesner, G. Camenisch, R. H. Wenger, and D. M. Katschinski
A Dominant-Negative Isoform of Hypoxia-Inducible Factor-1{alpha} Specifically Expressed in Human Testis
Biol Reprod,
July 1, 2004;
71(1):
331 - 339.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Uchida, F. Rossignol, M. A. Matthay, R. Mounier, S. Couette, E. Clottes, and C. Clerici
Prolonged Hypoxia Differentially Regulates Hypoxia-inducible Factor (HIF)-1{alpha} and HIF-2{alpha} Expression in Lung Epithelial Cells: IMPLICATION OF NATURAL ANTISENSE HIF-1{alpha}
J. Biol. Chem.,
April 9, 2004;
279(15):
14871 - 14878.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.A. Palladino, J.D. Powell, N. Korah, and L. Hermo
Expression and Localization of Hypoxia-Inducible Factor-1 Subunits in the Adult Rat Epididymis
Biol Reprod,
April 1, 2004;
70(4):
1121 - 1130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Makino, H. Nakamura, E. Ikeda, K. Ohnuma, K. Yamauchi, Y. Yabe, L. Poellinger, Y. Okada, C. Morimoto, and H. Tanaka
Hypoxia-Inducible Factor Regulates Survival of Antigen Receptor-Driven T Cells
J. Immunol.,
December 15, 2003;
171(12):
6534 - 6540.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Ma, L. Tessarollo, S.-B. Hong, M. Baba, E. Southon, T. C. Back, S. Spence, C. G. Lobe, N. Sharma, G. W. Maher, et al.
Hepatic Vascular Tumors, Angiectasis in Multiple Organs, and Impaired Spermatogenesis in Mice with Conditional Inactivation of the VHL Gene
Cancer Res.,
September 1, 2003;
63(17):
5320 - 5328.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. B. Freeburg, B. Robert, P. L. St. John, and D. R. Abrahamson
Podocyte Expression of Hypoxia-Inducible Factor (HIF)-1 and HIF-2 during Glomerular Development
J. Am. Soc. Nephrol.,
April 1, 2003;
14(4):
927 - 938.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Daikoku, H. Matsumoto, R. A. Gupta, S. K. Das, M. Gassmann, R. N. DuBois, and S. K. Dey
Expression of Hypoxia-inducible Factors in the Peri-implantation Mouse Uterus Is Regulated in a Cell-specific and Ovarian Steroid Hormone-dependent Manner. EVIDENCE FOR DIFFERENTIAL FUNCTION OF HIFs DURING EARLY PREGNANCY
J. Biol. Chem.,
February 21, 2003;
278(9):
7683 - 7691.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Powell, R. Elshtein, D. J. Forest, and M. A. Palladino
Stimulation of Hypoxia-Inducible Factor-1 Alpha (HIF-1{alpha}) Protein in the Adult Rat Testis Following Ischemic Injury Occurs Without an Increase in HIF-1{alpha} Messenger RNA Expression
Biol Reprod,
September 1, 2002;
67(3):
995 - 1002.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. H. WENGER
Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression
FASEB J,
August 1, 2002;
16(10):
1151 - 1162.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. H. Marti, D. M. Katschinski, K. F. Wagner, L. Schaffer, B. Stier, and R. H. Wenger
Isoform-Specific Expression of Hypoxia-Inducible Factor-1{alpha} During the Late Stages of Mouse Spermiogenesis
Mol. Endocrinol.,
February 1, 2002;
16(2):
234 - 243.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. M. STROKA, T. BURKHARDT, I. DESBAILLETS, R. H. WENGER, D. A. H. NEIL, C. BAUER, M. GASSMANN, and D. CANDINAS
HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia
FASEB J,
November 1, 2001;
15(13):
2445 - 2453.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Wenger
Mammalian oxygen sensing, signalling and gene regulation
J. Exp. Biol.,
January 4, 2000;
203(8):
1253 - 1263.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. BICHET, R. H. WENGER, G. CAMENISCH, A. ROLFS, W. EHLEBEN, T. PORWOL, H. ACKER, J. FANDREY, C. BAUER, and M. GASSMANN
Oxygen tension modulates ß-globin switching in embryoid bodies
FASEB J,
February 1, 1999;
13(2):
285 - 295.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
L. M. Neckers
aHIF: the Missing Link Between HIF-1 and VHL?
J Natl Cancer Inst,
January 20, 1999;
91(2):
106 - 107.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Lukashev, C. Caldwell, A. Ohta, P. Chen, and M. Sitkovsky
Differential Regulation of Two Alternatively Spliced Isoforms of Hypoxia-inducible Factor-1alpha in Activated T Lymphocytes
J. Biol. Chem.,
December 21, 2001;
276(52):
48754 - 48763.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
