Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1β

Yun Bai, Marco Pontoglio, Thomas Hiesberger, Angus M. Sinclair, Peter Igarashi

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Kidney-specific cadherin (Ksp-cadherin) is a tissue-specific member of the cadherin family that is expressed exclusively in the kidney and developing genitourinary tract. Recent studies have shown that the proximal 250 bp of the Ksp-cadherin gene promoter are sufficient to direct tissue-specific gene expression in vivo and in vitro. The proximal 120 bp of the promoter are evolutionarily conserved between mouse and human and contain a DNase I hypersensitive site that is kidney cell specific. At position -55, the promoter contains a consensus recognition site for hepatocyte nuclear factor-1 (HNF-1). Mutations of the consensus HNF-1 site and downstream GC-boxes inhibit promoter activity in transfected cells. HNF-1α and HNF-1β bind specifically to the -55 site, and both proteins transactivate the promoter directly. Expression of Ksp-cadherin is not altered in the kidneys of HNF-1α-deficient mice. However, expression of a gain-of-function HNF-1β mutant stimulates Ksp-cadherin promoter activity in transfected cells, whereas expression of a dominant-negative mutant inhibits activity. These studies identify Ksp-cadherin as the first kidney-specific promoter that has been shown to be regulated by HNF-1β. Mutations of HNF-1β, as occur in humans with inherited renal cysts and diabetes, may cause dysregulated Ksp-cadherin promoter activity.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume283
Issue number4 52-4
StatePublished - Oct 2002

Fingerprint

Hepatocyte Nuclear Factor 1
Kidney
Genes
Mutation
K cadherin
Deoxyribonuclease I
Cadherins
Cysts
Consensus
Gene Expression

Keywords

  • Deoxyribonuclease hypersensitive sites
  • Kidney-specific gene regulation
  • Maturity-onset diabetes of the young
  • Mouse inner medullary collecting duct-3 cells
  • Transcription factor

ASJC Scopus subject areas

  • Physiology

Cite this

Bai, Y., Pontoglio, M., Hiesberger, T., Sinclair, A. M., & Igarashi, P. (2002). Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1β. American Journal of Physiology - Renal Physiology, 283(4 52-4).

Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1β. / Bai, Yun; Pontoglio, Marco; Hiesberger, Thomas; Sinclair, Angus M.; Igarashi, Peter.

In: American Journal of Physiology - Renal Physiology, Vol. 283, No. 4 52-4, 10.2002.

Research output: Contribution to journalArticle

Bai, Y, Pontoglio, M, Hiesberger, T, Sinclair, AM & Igarashi, P 2002, 'Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1β', American Journal of Physiology - Renal Physiology, vol. 283, no. 4 52-4.
Bai, Yun ; Pontoglio, Marco ; Hiesberger, Thomas ; Sinclair, Angus M. ; Igarashi, Peter. / Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1β. In: American Journal of Physiology - Renal Physiology. 2002 ; Vol. 283, No. 4 52-4.
@article{f569e2676fc24780b5c7e13b1423cc85,
title = "Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1β",
abstract = "Kidney-specific cadherin (Ksp-cadherin) is a tissue-specific member of the cadherin family that is expressed exclusively in the kidney and developing genitourinary tract. Recent studies have shown that the proximal 250 bp of the Ksp-cadherin gene promoter are sufficient to direct tissue-specific gene expression in vivo and in vitro. The proximal 120 bp of the promoter are evolutionarily conserved between mouse and human and contain a DNase I hypersensitive site that is kidney cell specific. At position -55, the promoter contains a consensus recognition site for hepatocyte nuclear factor-1 (HNF-1). Mutations of the consensus HNF-1 site and downstream GC-boxes inhibit promoter activity in transfected cells. HNF-1α and HNF-1β bind specifically to the -55 site, and both proteins transactivate the promoter directly. Expression of Ksp-cadherin is not altered in the kidneys of HNF-1α-deficient mice. However, expression of a gain-of-function HNF-1β mutant stimulates Ksp-cadherin promoter activity in transfected cells, whereas expression of a dominant-negative mutant inhibits activity. These studies identify Ksp-cadherin as the first kidney-specific promoter that has been shown to be regulated by HNF-1β. Mutations of HNF-1β, as occur in humans with inherited renal cysts and diabetes, may cause dysregulated Ksp-cadherin promoter activity.",
keywords = "Deoxyribonuclease hypersensitive sites, Kidney-specific gene regulation, Maturity-onset diabetes of the young, Mouse inner medullary collecting duct-3 cells, Transcription factor",
author = "Yun Bai and Marco Pontoglio and Thomas Hiesberger and Sinclair, {Angus M.} and Peter Igarashi",
year = "2002",
month = "10",
language = "English (US)",
volume = "283",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4 52-4",

}

TY - JOUR

T1 - Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1β

AU - Bai, Yun

AU - Pontoglio, Marco

AU - Hiesberger, Thomas

AU - Sinclair, Angus M.

AU - Igarashi, Peter

PY - 2002/10

Y1 - 2002/10

N2 - Kidney-specific cadherin (Ksp-cadherin) is a tissue-specific member of the cadherin family that is expressed exclusively in the kidney and developing genitourinary tract. Recent studies have shown that the proximal 250 bp of the Ksp-cadherin gene promoter are sufficient to direct tissue-specific gene expression in vivo and in vitro. The proximal 120 bp of the promoter are evolutionarily conserved between mouse and human and contain a DNase I hypersensitive site that is kidney cell specific. At position -55, the promoter contains a consensus recognition site for hepatocyte nuclear factor-1 (HNF-1). Mutations of the consensus HNF-1 site and downstream GC-boxes inhibit promoter activity in transfected cells. HNF-1α and HNF-1β bind specifically to the -55 site, and both proteins transactivate the promoter directly. Expression of Ksp-cadherin is not altered in the kidneys of HNF-1α-deficient mice. However, expression of a gain-of-function HNF-1β mutant stimulates Ksp-cadherin promoter activity in transfected cells, whereas expression of a dominant-negative mutant inhibits activity. These studies identify Ksp-cadherin as the first kidney-specific promoter that has been shown to be regulated by HNF-1β. Mutations of HNF-1β, as occur in humans with inherited renal cysts and diabetes, may cause dysregulated Ksp-cadherin promoter activity.

AB - Kidney-specific cadherin (Ksp-cadherin) is a tissue-specific member of the cadherin family that is expressed exclusively in the kidney and developing genitourinary tract. Recent studies have shown that the proximal 250 bp of the Ksp-cadherin gene promoter are sufficient to direct tissue-specific gene expression in vivo and in vitro. The proximal 120 bp of the promoter are evolutionarily conserved between mouse and human and contain a DNase I hypersensitive site that is kidney cell specific. At position -55, the promoter contains a consensus recognition site for hepatocyte nuclear factor-1 (HNF-1). Mutations of the consensus HNF-1 site and downstream GC-boxes inhibit promoter activity in transfected cells. HNF-1α and HNF-1β bind specifically to the -55 site, and both proteins transactivate the promoter directly. Expression of Ksp-cadherin is not altered in the kidneys of HNF-1α-deficient mice. However, expression of a gain-of-function HNF-1β mutant stimulates Ksp-cadherin promoter activity in transfected cells, whereas expression of a dominant-negative mutant inhibits activity. These studies identify Ksp-cadherin as the first kidney-specific promoter that has been shown to be regulated by HNF-1β. Mutations of HNF-1β, as occur in humans with inherited renal cysts and diabetes, may cause dysregulated Ksp-cadherin promoter activity.

KW - Deoxyribonuclease hypersensitive sites

KW - Kidney-specific gene regulation

KW - Maturity-onset diabetes of the young

KW - Mouse inner medullary collecting duct-3 cells

KW - Transcription factor

UR - http://www.scopus.com/inward/record.url?scp=0036783560&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036783560&partnerID=8YFLogxK

M3 - Article

C2 - 12217876

AN - SCOPUS:0036783560

VL - 283

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 4 52-4

ER -