Document Detail


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.
MedLine Citation:
PMID:  23013251     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
U M Paredes; J P Quinn; U M D'Souza
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-07
Journal Detail:
Title:  Genes, brain, and behavior     Volume:  12     ISSN:  1601-183X     ISO Abbreviation:  Genes Brain Behav.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-25     Completed Date:  2013-08-09     Revised Date:  2013-09-18    
Medline Journal Info:
Nlm Unique ID:  101129617     Medline TA:  Genes Brain Behav     Country:  England    
Other Details:
Languages:  eng     Pagination:  282-7     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
Affiliation:
MRC Centre for Social, Genetic and Developmental Psychiatry (SGDP), Institute of Psychiatry, King's College, University of London, London. ursula.paredes@zoo.ox.ac.uk
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MeSH Terms
Descriptor/Qualifier:
5' Flanking Region*
Alleles
Animals
Brain / cytology,  metabolism
Cell Line
Genes, Reporter
Humans
Luciferases / genetics,  metabolism
Male
Minisatellite Repeats*
Neurons / metabolism*
Polymorphism, Genetic
Rats
Rats, Wistar
Receptors, Dopamine D4 / genetics*,  metabolism
Repressor Proteins / metabolism
Transcription, Genetic*
Upstream Stimulatory Factors / metabolism
Chemical
Reg. No./Substance:
0/CCCTC-binding factor; 0/DRD4 protein, human; 0/Repressor Proteins; 0/Upstream Stimulatory Factors; 137750-34-6/Receptors, Dopamine D4; EC 1.13.12.-/Luciferases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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