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 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.
Michelhaugh
S K
SK
Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, USA.
Fiskerstrand
C
C
Lovejoy
E
E
Bannon
M J
MJ
Quinn
J P
JP
D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D017930:Genes, Reporter / Q000235:genetics; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018598:Minisatellite Repeats / Q000235:genetics*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins; D014158:Transcription, Genetic / Q000235:genetics*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493215:Slc6a3 protein, mouse; C493216:Slc6a3 protein, rat; C493231:Slc6a4 protein, mouse; C493232:Slc6a4 protein, rat; D049452:Green Fluorescent Proteins; D000445:Aldehyde Oxidoreductases; C050832:ethylmalonate-semialdehyde dehydrogenase; D004298:Dopamine