Allele‐specific transcriptional activity of the variable number of tandem repeats in 5′ region of the DRD4 gene is stimulus specific in human neuronal cells
Abstract
The dopamine receptor D4 (DRD4) gene includes several variable number of tandem repeat loci that have been suggested to modulate DRD4 gene expression patterns. Previous studies showed differential basal activity of the two most common variants of a tandem repeat (120 bp per repeat unit) located in the 5' region adjacent to the DRD4 promoter in human cell lines. In this communication, we further characterized the ability of this polymorphic repeat to elicit tissue-, allele- and stimuli-specific transcriptional activity in vitro. The short and long variants of the DRD4 5' tandem repeat were cloned into a luciferase reporter gene construct containing the SV40 promoter. The luciferase constructs were cotransfected with expression vectors of two ubiquitously expressed human transcription factors (TFs), CCCTC-binding factor (CTCF) and upstream stimulatory factor 2 (USF2), into human cell lines and primary cultures of neonate rat cortex and luciferase activity measured. Overexpression with these TFs resulted in differential cell- and allele-specific transcriptional activities of the luciferase constructs. The results of our experiments show that variants of this tandem repeat in the 5' promoter of the DRD4 gene will direct differential reporter gene transcriptional activity in a cell-type-specific manner dependent on the signal pathways activated.
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Polymorphic cis-regulatory elements have been shown to affect CTCF binding and DNA looping.
“Polymorphic cis-REs have been shown to influence CTCF binding (71, 72) and DNA looping (73).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [71]
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“Polymorphic cis-REs have been shown to influence CTCF binding (70,71) and DNA looping (72).”
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- Authors
- Paredes, U. M., Quinn, J. P., & D'Souza, U. M.
- Affiliations
- University of London (GB)
- University of Liverpool (GB)
- Corresponding author
- Paredes, U. M.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2012-11-07
- Volume
- 12
- Issue
- 2
- Pages
- 282-287
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- OpenAlex
- W1849591313
- Cited by
- 10
- References
- 27
- Citations by year
- 2020: 1 · 2016: 3 · 2015: 4 · 2014: 2
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genes Brain & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DRD4 gene, variable number tandem repeats, allele-specific transcription, dopamine D4 receptor, CTCF, USF2, transcription factors, cell type-specific gene expression, signaling pathways, luciferase reporter
- MeSH terms
- CCCTC-Binding Factor, Alleles, Animals, Brain, Cell Line, Humans, Luciferases, Male, Neurons, Polymorphism, Genetic, Repressor Proteins, Transcription, Genetic, Rats, Wistar, Genes, Reporter, Minisatellite Repeats, 5' Flanking Region, Receptors, Dopamine D4, Rats, Upstream Stimulatory Factors
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