Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1β
| العنوان: | Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1β |
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| المؤلفون: | Peter Igarashi, Angus M. Sinclair, Thomas Hiesberger, Yun Bai, Marco Pontoglio |
| المصدر: | Scopus-Elsevier Experts@Minnesota |
| بيانات النشر: | American Physiological Society, 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Physiology, DNA Mutational Analysis, Molecular Sequence Data, Mutant, Biology, Kidney, Transfection, digestive system, Mice, Genes, Reporter, Gene expression, Animals, Deoxyribonuclease I, Humans, Hepatocyte Nuclear Factor 1-alpha, Promoter Regions, Genetic, Transcription factor, Cells, Cultured, Conserved Sequence, Hepatocyte Nuclear Factor 1-beta, Cell Nucleus, Mice, Knockout, Base Sequence, Cadherin, Nucleotide Mapping, Nuclear Proteins, Promoter, Blotting, Northern, Cadherins, Molecular biology, DNA-Binding Proteins, Hepatocyte nuclear factors, Gene Expression Regulation, Hepatocyte Nuclear Factor 1, Mutation, embryonic structures, DNase I hypersensitive site, Plasmids, Protein Binding, Transcription Factors |
| الوصف: | 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. |
| تدمد: | 1522-1466 1931-857X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f118d2388262230d2195c55463bcac9Test https://doi.org/10.1152/ajprenal.00128.2002Test |
| رقم الانضمام: | edsair.doi.dedup.....4f118d2388262230d2195c55463bcac9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221466 1931857X |
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