caa a22 4500 445861827 CHVBK 20180317145445.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s00439-011-0949-1 doi (NATIONALLICENCE)springer-10.1007/s00439-011-0949-1 Transcriptional control of the human glucocorticoid receptor: identification and analysis of alternative promoter regions [Elektronische Daten] [Lei Cao-Lei, Salomon Leija, Robert Kumsta, Stefan Wüst, Jobst Meyer, Jonathan Turner, Claude Muller] Glucocorticoid receptor levels are thought to be controlled by multiple alternative first exons. Seven of these exons are located in an upstream CpG island. In this study, we investigated the promoter activity of the intronic regions between these exons, and their susceptibility to CpG methylation and sequence variability. The seven promoters were cloned into luciferase reporter genes, and their activity measured in ten cell lines. CpG islands of 221 donors were genotyped and the effects of these SNPs were investigated in a reporter gene assay. We showed that each of the first exons was independently controlled by a unique promoter located directly upstream. Promoter activities were cell type-specific, and varied considerably between cell types. Irrespective of the cell type, in vitro methylation effectively silenced all reporter constructs. Eleven SNPs were observed within the CpG island of 221 donors, and a new promoter-specific haplotype was revealed. Four of the minor alleles reduced the reporter gene activity, with cell type specific effects. This complexity within the CpG island helps to explain the variable, tissue-specific transcriptional control of the GR, and provides insight into the mechanisms underlying tissue specific deregulation of GR levels. Springer-Verlag, 2011 Cao-Lei Lei Institute of Immunology, CRP-Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, 1011, Luxembourg, Grand Duchy of Luxembourg aut Leija Salomon Institute of Immunology, CRP-Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, 1011, Luxembourg, Grand Duchy of Luxembourg aut Kumsta Robert King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK aut Wüst Stefan Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, J5, 68159, Mannheim, Germany aut Meyer Jobst Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, 54290, Trier, Germany aut Turner Jonathan Institute of Immunology, CRP-Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, 1011, Luxembourg, Grand Duchy of Luxembourg aut Muller Claude Institute of Immunology, CRP-Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, 1011, Luxembourg, Grand Duchy of Luxembourg aut Human Genetics Springer-Verlag 129/5(2011-05-01), 533-543 0340-6717 129:5<533 2011 129 439 https://doi.org/10.1007/s00439-011-0949-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-0949-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cao-Lei Lei Institute of Immunology, CRP-Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, 1011, Luxembourg, Grand Duchy of Luxembourg aut NATIONALLICENCE 700 1- Leija Salomon Institute of Immunology, CRP-Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, 1011, Luxembourg, Grand Duchy of Luxembourg aut NATIONALLICENCE 700 1- Kumsta Robert King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK aut NATIONALLICENCE 700 1- Wüst Stefan Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, J5, 68159, Mannheim, Germany aut NATIONALLICENCE 700 1- Meyer Jobst Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, 54290, Trier, Germany aut NATIONALLICENCE 700 1- Turner Jonathan Institute of Immunology, CRP-Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, 1011, Luxembourg, Grand Duchy of Luxembourg aut NATIONALLICENCE 700 1- Muller Claude Institute of Immunology, CRP-Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, 1011, Luxembourg, Grand Duchy of Luxembourg aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/5(2011-05-01), 533-543 0340-6717 129:5<533 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer