Characterization and functional analyses of the human G protein-coupled receptor kinase 4 gene promoter

Hypertension
Sandra HasenkampEva Brand

Abstract

The G protein-coupled receptor kinase 4 is involved in renal sodium handling and blood pressure regulation. Missense variants have already been tested functionally and are associated with hypertension, but no data on promoter analyses are yet available. We scanned 94 hypertensive white subjects for genetic variation and performed promoter reporter gene analyses in HEK293T, COS7, and SaOs-2 cells. Transient transfections with various full lengths and wild-type deletion constructs revealed that 1851 bp of the flanking region and 275 bp of the 5'-untranslated region were sufficient for transcriptional activities and composed a powerful cis-active element in the distal 293 bp. The -1702T and +2T alleles resulted in drastic general reductions of promoter function, whereas an activity increasing effect of +268C was cell type specific. Electrophoretic mobility-shift assay, supershift, and cotransfection analyses of transcription factor binding sites predicted in silico (Alibaba2.1/Transfac7) resulted in allele-specific binding patterns of nuclear proteins and identified the participation of CCAAT/enhancer-binding protein transcription factor family members. The G protein-coupled receptor kinase 4 core promoter resides in the first 185...Continue Reading

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Citations

Aug 20, 2008·Hypertension·Peter A Doris
Nov 19, 2011·Molecular Ecology·Larissa M Williams, Marjorie F Oleksiak
Jul 9, 2016·Journal of the American Heart Association·Jian YangChunyu Zeng
Apr 15, 2015·Hypertension·Jian YangChunyu Zeng
Aug 7, 2017·Current Hypertension Reports·Andrew C TiuVan Anthony M Villar

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