Pancreatic islet expression studies and polymorphic DNA markers in the genes encoding hepatocyte nuclear factor-3alpha, -3beta, -3gamma, -4gamma, and -6.
The genes encoding the functionally related hepatocyte nuclear factors HNF-1alpha and HNF-4alpha play a critical role in normal pancreatic beta-cell function. Mutations in these liver-enriched transcription factors result in two forms of early-onset type 2 diabetes (maturity-onset diabetes of the young [MODY]), MODY3 and MODY1, which are characterized by impaired glucose-stimulated insulin secretion, early disease onset, and autosomal dominant inheritance. The transcriptional hierarchy of HNFs suggests that other proteins of the regulatory cascade might be responsible for other forms of MODY and/or late-onset type 2 diabetes. In this study, we show that HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 are expressed in pancreatic beta-cells. We report the identification and characterization of simple tandem repeat DNA polymorphisms in the genes encoding HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 and the mapping of HNF-6 to chromosome bands 15q21.1-21.2 by fluorescence in situ hybridization. These markers will be useful to study the role of genetic variation in these genes in the pathogenesis of type 2 diabetes.
Vaisse
C
C
Laboratory of Metabolic Diseases, Rockefeller University, New York, New York 10021, USA.
Kim
J
J
Espinosa
R
R
Le Beau
M M
MM
Stoffel
M
M
D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051541:Hepatocyte Nuclear Factor 3-alpha; D051542:Hepatocyte Nuclear Factor 3-beta; D051543:Hepatocyte Nuclear Factor 3-gamma; D051557:Hepatocyte Nuclear Factor 4; D051559:Hepatocyte Nuclear Factor 6; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007515:Islets of Langerhans / Q000737:chemistry* / Q000166:cytology; D008099:Liver / Q000737:chemistry; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D013154:Spleen / Q000737:chemistry; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017931:DNA Primers; D004268:DNA-Binding Proteins; C496499:FOXA1 protein, human; C496502:FOXA2 protein, human; C496505:FOXA3 protein, human; D005819:Genetic Markers; C496487:HNF1A protein, human; C496495:HNF1B protein, human; C496592:HNF4A protein, human; C496597:HNF4G protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051541:Hepatocyte Nuclear Factor 3-alpha; D051557:Hepatocyte Nuclear Factor 4; D051559:Hepatocyte Nuclear Factor 6; D018398:Homeodomain Proteins; C403128:MLX protein, human; D009687:Nuclear Proteins; C496605:ONECUT1 protein, human; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051543:Hepatocyte Nuclear Factor 3-gamma; D051542:Hepatocyte Nuclear Factor 3-beta; D051539:Hepatocyte Nuclear Factor 1-beta