|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 281, Issue 46, 35296-35304, November 17, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The Human Renin Kidney Enhancer Is Required to Maintain Base-line Renin Expression but Is Dispensable for Tissue-specific, Cell-specific, and Regulated Expression*
¶1
From the
Molecular and Cellular Biology Graduate Program, Departments of Internal Medicine and ¶Molecular Physiology & Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242
Renin is the rate-limiting enzyme in the renin-angiotensin system and thus dictates the level of the pressor hormone angiotensin-II. The classical site of renin expression and secretion is the renal juxtaglomerular cell, where its expression is tightly regulated by physiological cues. An evolutionarily conserved transcriptional enhancer located 11 kb upstream of the human RENIN gene has been reported to markedly enhance transcription in renin expressing cells in vitro. However, its importance in vivo remains unclear. We tested whether this enhancer is required for appropriate tissue- and cell-specific expression, or for physiological regulation of the human RENIN gene. To accomplish this, we used a retrofitting technique employing homologous recombination in bacteria to delete the enhancer from a 160-kb P1-artificial chromosome containing human RENIN, two upstream genes and one downstream gene, and then generated two lines of transgenic mice. We previously showed that human renin expression in transgenic mice containing the wild type construct is tightly regulated as is expression of the linked genes. Deletion of the enhancer had no effect on tissue-specific expression of human RENIN, but using the downstream gene as an internal control, found that human RENIN mRNA levels were 3-10-fold decreased compared with constructs containing the enhancer. Despite this decrease in expression, renin protein remained localized to renal juxtaglomerular cells and was appropriately regulated by cues that either increase or decrease expression of renin. Our results suggest that sequences other than the enhancer may be necessary for tissue-specific, cell-specific, and regulated expression of human RENIN.
Received for publication, August 22, 2006 , and in revised form, September 20, 2006.
* This work was supported National Institutes of Health Grants HL48058, HL61446, and HL55006. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed: 3181B Medical Education and Biomedical Research Facility, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242. Tel.: 319-335-7604; Fax: 319-353-5350; E-mail: curt-sigmund{at}uiowa.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Itani, X. Liu, E. H. Sarsour, P. C. Goswami, E. Born, H. L. Keen, and C. D. Sigmund Regulation of Renin Gene Expression by Oxidative Stress Hypertension, June 1, 2009; 53(6): 1070 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Neubauer, K. Machura, M. Chen, L. S. Weinstein, M. Oppermann, M. L. Sequeira-Lopez, R. A. Gomez, J. Schnermann, H. Castrop, A. Kurtz, et al. Development of vascular renin expression in the kidney critically depends on the cyclic AMP pathway Am J Physiol Renal Physiol, May 1, 2009; 296(5): F1006 - F1012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. T. Glenn, C. A. Jones, L. Pan, and K. W. Gross In vivo analysis of key elements within the renin regulatory region Physiol Genomics, November 12, 2008; 35(3): 243 - 253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Beyer, W. J. de Lange, C. M. Halabi, M. L. Modrick, H. L. Keen, F. M. Faraci, and C. D. Sigmund Endothelium-Specific Interference With Peroxisome Proliferator Activated Receptor Gamma Causes Cerebral Vascular Dysfunction in Response to a High-Fat Diet Circ. Res., September 12, 2008; 103(6): 654 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhou, E. T. Weatherford, X. Liu, E. Born, H. L. Keen, and C. D. Sigmund Dysregulated human renin expression in transgenic mice carrying truncated genomic constructs: evidence supporting the presence of insulators at the renin locus Am J Physiol Renal Physiol, September 1, 2008; 295(3): F642 - F653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhou and C. D. Sigmund Chorionic enhancer is dispensable for regulated expression of the human renin gene Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R279 - R287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. T. Todorov, M. Desch, N. Schmitt-Nilson, A. Todorova, and A. Kurtz Peroxisome Proliferator-Activated Receptor-{gamma} Is Involved in the Control of Renin Gene Expression Hypertension, November 1, 2007; 50(5): 939 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Weatherford, H. Itani, H. L. Keen, and C. D. Sigmund Is Peroxisome Proliferator-Activated Receptor-{gamma} a New "Pal" of Renin? Hypertension, November 1, 2007; 50(5): 844 - 846. [Full Text] [PDF]
|
|
|
|
|
|
M. A. Markus, C. Goy, D. J. Adams, F. J. Lovicu, and B. J. Morris Renin Enhancer Is Crucial for Full Response in Renin Expression to an In Vivo Stimulus Hypertension, November 1, 2007; 50(5): 933 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Itani, X. Liu, J. H. Pratt, and C. D. Sigmund Functional Characterization of Polymorphisms in the Kidney Enhancer of the Human Renin Gene Endocrinology, March 1, 2007; 148(3): 1424 - 1430. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |