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 Scopus citations

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)
Pages (from-to)F839-F851
JournalAmerican Journal of Physiology - Renal Physiology
Volume283
Issue number4 52-4
DOIs
StatePublished - Oct 2002

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
  • Urology

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