The dopamine transporter gene (SLC6A3) variable number of tandem repeats domain enhances transcription in dopamine neurons

The dopamine (DAT) and serotonin (SERT) transporter genes both contain variable number of tandem repeats (VNTR) in non‐coding gene regions which have been correlated with a predisposition to a variety of CNS disorders. There is considerable homology between individual DAT and SERT repeat DNA sequenc...

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Bibliographic Details
Published in:Journal of neurochemistry 2001-12, Vol.79 (5), p.1033-1038
Main Authors: Michelhaugh, Sharon K., Fiskerstrand, Carolyn, Lovejoy, Elizabeth, Bannon, Michael J., Quinn, John P.
Format: Article
Language:English
Subjects:
Aldehyde Oxidoreductases - metabolism
Animals
biolistic transfection
Biological and medical sciences
Carrier Proteins - metabolism
Cells, Cultured
Dopamine - physiology
Dopamine Plasma Membrane Transport Proteins
Fundamental and applied biological sciences. Psychology
gene expression
Genes, Reporter - genetics
GFP
Green Fluorescent Proteins
Humans
Immunohistochemistry
Luminescent Proteins
Membrane Glycoproteins - metabolism
Membrane Transport Proteins - genetics
Membrane Transport Proteins - metabolism
Mice
Minisatellite Repeats - genetics
Molecular and cellular biology
Molecular genetics
Nerve Tissue Proteins
Neurons - metabolism
organotypic slice culture
Protein Binding
Rats
Rats, Sprague-Dawley
Serotonin Plasma Membrane Transport Proteins
Transcription, Genetic - genetics
Transcription. Transcription factor. Splicing. Rna processing
VNTR
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Summary:The dopamine (DAT) and serotonin (SERT) transporter genes both contain variable number of tandem repeats (VNTR) in non‐coding gene regions which have been correlated with a predisposition to a variety of CNS disorders. There is considerable homology between individual DAT and SERT repeat DNA sequences, which is reflected in their ability to compete with each other for specific protein binding as demonstrated by electrophoretic mobility shift assay. The SERT VNTR has recently been shown to act as a transcriptional enhancer. Because of the similarities between SERT and DAT VNTRs, the DAT VNTR may also enhance transcription. This study demonstrates by lipid transfection into an immortalized dopaminergic cell line and biolistic transfection into dopamine neurons in neonatal rat midbrain slices that the human nine‐repeat DAT VNTR can enhance transcription. This enhancing activity suggests that the DAT VNTR may play a role in regulation of DAT gene expression.
ISSN:0022-3042
1471-4159
DOI:10.1046/j.1471-4159.2001.00647.x