Single nucleotide polymorphism analysis and functional characterization of the human Ah receptor (AhR) gene promoter
| Autor: | Hans-Martin Kauffmann, Dieter Schrenk, Hans-Joachim Schmitz, Judith Racky |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Genotype Transcription Genetic 5' Flanking Region Biophysics Gene Expression Transfection Polymorphism Single Nucleotide Biochemistry AH Receptor Regulatory region Cell Line Cohort Studies Genes Reporter Cell Line Tumor Gene expression Animals Humans RNA Messenger Cyclic AMP Response Element-Binding Protein Luciferases Promoter Regions Genetic Molecular Biology Gene Regulation of gene expression Genetics biology Promoter respiratory system Aryl hydrocarbon receptor Molecular biology Recombinant Proteins respiratory tract diseases Drosophila melanogaster Receptors Aryl Hydrocarbon Mutagenesis Site-Directed biology.protein Single nucleotide polymorphism analysis Female Gene Deletion |
| Zdroj: | Archives of Biochemistry and Biophysics. 421:91-98 |
| ISSN: | 0003-9861 |
| Popis: | The aryl hydrocarbon receptor (AhR) mediates biological and toxicological actions of e.g., halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. Although much is known about the biochemical and molecular mechanisms of AhR action, little is known about the control of the expression of the AhR gene itself. Therefore, we aimed at the identification and characterization of regions important for constitutive AhR gene expression. First, we screened 2.6 kb of the 5′-flanking region of the AhR gene in 91 healthy Caucasian volunteers for naturally occurring genetic variants. Seven variants were detected. However, they do not seem to influence AhR gene expression in lymphocytes. Using a 2.7 kb AhR promoter luciferase reporter gene construct and various deletion constructs, a putative regulatory region was identified and characterized further by electrophoretic mobility shift assays and site-directed mutagenesis. These investigations were confirmed by cotransfection experiments in Drosophila SL2 cells. The obtained results prove an involvement of Sp1 in AhR gene regulation. |
| Databáze: | OpenAIRE |
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