| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of 1 Pediatrics, 2 Internal Medicine, and 3 Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520; and 4 Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202
Kidney-specific
cadherin (Ksp-cadherin, cadherin 16) is a novel,
kidney-specific member of the cadherin superfamily that is expressed
exclusively in the basolateral membrane of renal tubular epithelial
cells. To characterize the Ksp-cadherin gene promoter, a 
bacteriophage clone containing 3.7 kb of the proximal 5' flanking region of the mouse Ksp-cadherin gene was isolated. The transcription initiation site was mapped by RNase protection assays and 5'
rapid amplification of cDNA ends, and a 709-bp intron was identified within the 5' untranslated region. The proximal 5' flanking
region was "TATA-less" but contained other consensus promoter
elements including an initiator (Inr), GC boxes, and a CAAT box.
Potential binding sites were identified for transcription factors that
are involved in tissue-specific gene expression including activator protein-2 (AP-2), hepatocyte nuclear factor-3 (HNF-3), basic
helix-loop-helix (bHLH) proteins, CCAAT/enhancer-binding protein
(C/EBP), and GATA factors. Transfection of luciferase reporter plasmids
containing 2.6 kb of the 5' flanking region markedly increased
luciferase activity in renal epithelial cells (MDCK and mIMCD-3) but
not in mesenchymal cells (NIH 3T3 and MMR1). Deletion analysis
identified an 82-bp region from 
31 to 113 that was
essential for promoter activity in transfected renal epithelial cells.
Electrophoretic mobility-shift assays showed that mIMCD-3 cells contain
nuclear proteins that bind to this region of the promoter. Mutational analysis showed that sequences within the HNF-3 consensus site and CAAT
box were involved in protein binding and promoter activity. We conclude
that the proximal 5' flanking region of the mouse Ksp-cadherin
gene contains an orientation-dependent promoter that is kidney
epithelial cell specific. The region of the promoter from 113 to
31 is required for transcriptional activity and contains binding
sites for nuclear proteins that are specifically expressed in renal
epithelial cells.
kidney specific; gene regulation; transcription factor; cell adhesion
This article has been cited by other articles:
|
|
 |
|
  M. Sakai, K. Tamura, Y. Tsurumi, Y. Tanaka, Y. Koide, M. Matsuda, T. Ishigami, M. Yabana, Y. Tokita, Y. Hiroi, et al. Expression of MAK-V/Hunk in renal distal tubules and its possible involvement in proliferative suppression Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1526 - F1536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Efrati, J. Arsentiev-Rozenfeld, and I. Zelikovic The human paracellin-1 gene (hPCLN-1): renal epithelial cell-specific expression and regulation Am J Physiol Renal Physiol, February 1, 2005; 288(2): F272 - F283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Bai, M. Pontoglio, T. Hiesberger, A. M. Sinclair, and P. Igarashi Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1beta Am J Physiol Renal Physiol, October 1, 2002; 283(4): F839 - F851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Shao, J. E. Johnson, J. A. Richardson, T. Hiesberger, and P. Igarashi A Minimal Ksp-Cadherin Promoter Linked to a Green Fluorescent Protein Reporter Gene Exhibits Tissue-Specific Expression in the Developing Kidney and Genitourinary Tract J. Am. Soc. Nephrol., July 1, 2002; 13(7): 1824 - 1836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Shao, S. Somlo, and P. Igarashi Epithelial-Specific Cre/lox Recombination in the Developing Kidney and Genitourinary Tract J. Am. Soc. Nephrol., July 1, 2002; 13(7): 1837 - 1846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yoshida, J. Yoshino, M. Hayashi, and T. Saruta Identification of a Renal Proximal Tubular Cell-Specific Enhancer in the Mouse 25-Hydroxyvitamin D 1{alpha}-Hydroxylase Gene J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1455 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Robert-Nicoud, M. Flahaut, J.-M. Elalouf, M. Nicod, M. Salinas, M. Bens, A. Doucet, P. Wincker, F. Artiguenave, J.-D. Horisberger, et al. Transcriptome of a mouse kidney cortical collecting duct cell line: Effects of aldosterone and vasopressin PNAS, February 15, 2001; (2001) 51603198. [Abstract] [Full Text]
|
|
|
|
|
|
P. Igarashi, C. S. Shashikant, R. B. Thomson, D. A. Whyte, S. Liu-Chen, F. H. Ruddle, and P. S. Aronson Ksp-cadherin gene promoter. II. Kidney-specific activity in transgenic mice Am J Physiol Renal Physiol, October 1, 1999; 277(4): F599 - F610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Taniyama, K. Sato, A. Sugawara, A. Uruno, Y. Ikeda, M. Kudo, S. Ito, and K. Takeuchi Renal Tubule-specific Transcription and Chromosomal Localization of Rat Thiazide-sensitive Na-Cl Cotransporter Gene J. Biol. Chem., July 6, 2001; 276(28): 26260 - 26268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Robert-Nicoud, M. Flahaut, J.-M. Elalouf, M. Nicod, M. Salinas, M. Bens, A. Doucet, P. Wincker, F. Artiguenave, J.-D. Horisberger, et al. Transcriptome of a mouse kidney cortical collecting duct cell line: Effects of aldosterone and vasopressin PNAS, February 27, 2001; 98(5): 2712 - 2716. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
