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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

Paredes, U. M. ; Quinn, J. P. ; D'Souza, U. M.

Genes, brain and behavior, 2013-03, Vol.12 (2), p.282-287 [Periódico revisado por pares]

Oxford, UK: Blackwell Publishing Ltd

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Título:
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
Autor: Paredes, U. M. ; Quinn, J. P. ; D'Souza, U. M.
Assuntos: 5' Flanking Region ; Alleles ; Animals ; Behavioral psychophysiology ; Biological and medical sciences ; Brain - cytology ; Brain - metabolism ; CCCTC-Binding Factor ; Cell Line ; Dopamine receptor ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Genes, Reporter ; Humans ; Luciferases - genetics ; Luciferases - metabolism ; Male ; Minisatellite Repeats ; neuronal cultures ; Neurons - metabolism ; Neurotransmission and behavior ; Polymorphism, Genetic ; Proteins ; Psychology. Psychoanalysis. Psychiatry ; Psychology. Psychophysiology ; Rats ; Rats, Wistar ; Receptors, Dopamine D4 - genetics ; Receptors, Dopamine D4 - metabolism ; Repressor Proteins - metabolism ; Simian virus 40 ; Transcription, Genetic ; Upstream Stimulatory Factors - metabolism ; VNTR
É parte de: Genes, brain and behavior, 2013-03, Vol.12 (2), p.282-287
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
Descrição: 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. The DRD4 5′ VNTR variants exhibit stimulus‐specific transcriptional activity in human neuronal cell types.
Editor: Oxford, UK: Blackwell Publishing Ltd
Idioma: Inglês

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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

Paredes, U. M. ; Quinn, J. P. ; D'Souza, U. M.

Oxford, UK: Blackwell Publishing Ltd

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