例如:"lncRNA", "apoptosis", "WRKY"

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

Am. J. Physiol. Renal Physiol.2002 Oct;283(4):F839-51. doi:10.1152/ajprenal.00128.2002
Yun Bai 1 , Marco Pontoglio , Thomas Hiesberger , Angus M Sinclair , Peter Igarashi
Yun Bai 1 , Marco Pontoglio , Thomas Hiesberger , Angus M Sinclair , Peter Igarashi

[No authors listed]

Author information
  • 1 Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 75390, USA.

摘要


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-1alpha and HNF-1beta 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-1alpha-deficient mice. However, expression of a gain-of-function HNF-1beta 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-1beta. Mutations of HNF-1beta, as occur in humans with inherited renal cysts and diabetes, may cause dysregulated Ksp-cadherin promoter activity.