Journal article
Functional analysis of a novel human serotonin transporter gene promoter in immortalized raphe cells
Brain research. Molecular brain research., v 68(1)
1999
PMID: 10320791
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
To investigate the structural basis for genetic regulation of the human serotonin transporter gene, a 1.8 kb fragment upstream to the cap site was cloned and sequenced. The promoter possesses a polymorphic repeat region with 16 and 14 repeats, respectively. Both were cloned and characterized. The promoter sequence revealed an internal 379 bp fragment not reported in previous publications. This novel fragment contains consensus sequences for several transcription factors including SpI and GATA. DNA from 48 unrelated individuals was PCR amplified, in this region, to test for allelic variations. All were found to possess the additional 379 bp fragment. The integrity of the promoter was furthermore confirmed by genomic Southern blotting. The promoter activity was analyzed by reporter gene assays in neuronal and non-neuronal serotonergic cell lines. In immortalized serotonergic raphe neurons, RN46A, three
cis-acting, cell specific, activating elements and a silencer were located. One of the activators and the silencer are located in the repeat region and one activator is positioned in the novel fragment. A fourth activating element was found to be active in both RN46A cells and in a non-neuronal serotonergic cell line, JAR. A 3.5 kb fragment from intron 1 was cloned and found to possess cell specific activity in JAR cells indicating the presence of an alternative promoter in intron 1.
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Details
- Title
- Functional analysis of a novel human serotonin transporter gene promoter in immortalized raphe cells
- Creators
- Ole V Mortensen - Department of Biological Psychiatry, Psychiatric University Hospital, Skovagervej 2, 8240 Risskov, DenmarkMads Thomassen - Department of Biological Psychiatry, Psychiatric University Hospital, Skovagervej 2, 8240 Risskov, DenmarkMads B Larsen - Department of Biological Psychiatry, Psychiatric University Hospital, Skovagervej 2, 8240 Risskov, DenmarkScott R Whittemore - Department of Neurological Surgery, University of Louisville School of Medicine 210 E. Gray St., Suite 1102, Louisville, KY 40056, USAOve Wiborg - Department of Biological Psychiatry, Psychiatric University Hospital, Skovagervej 2, 8240 Risskov, Denmark
- Publication Details
- Brain research. Molecular brain research., v 68(1)
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000080360700014
- Scopus ID
- 2-s2.0-0033532309
- Other Identifier
- 991014877992104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences