2011
DOI: 10.1111/j.1369-1600.2010.00288.x View full text |Buy / Rent full text
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Abstract: We demonstrated that the genotype of the variable number tandem repeats (VNTRs) in the linked polymorphic region (LPR) of the 5' promoter and in the intron 2 (Stin2) transcriptional regulatory domains of the serotonin transporter SLC6A4 gene determined its promoter interactions with transcription factors and co-activators in response to cocaine in the JAr cell line. The LPR variants contain 14 (short, s) or 16 (long, l) copies of a 22-23 bp repeat element, whereas the Stin2 VNTR exists as three variants contai… Show more

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“…The data on the central TR/VNTR indicated they support distinct transcriptional properties dependent on cell type. This is consistent with the action of VNTRs we have previously observed in the human serotonin and dopamine transporter genes [28,31,34]. We would expect that different complements of transcription factors present in both these cell lines are responsible for the activity of the reporter gene directed by the TR/VNTR.…”
Section: Discussionsupporting
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“…The data on the central TR/VNTR indicated they support distinct transcriptional properties dependent on cell type. This is consistent with the action of VNTRs we have previously observed in the human serotonin and dopamine transporter genes [28,31,34]. We would expect that different complements of transcription factors present in both these cell lines are responsible for the activity of the reporter gene directed by the TR/VNTR.…”
Section: Discussionsupporting
“…SVAs contain large domains of repetitive DNA (VNTRs) similar in copy number and size of individual repeats to those, we and others, have found to direct differential tissue specific and stimulus inducible gene expression in many other genes [28-35]. This differential regulator property has been correlated with copy number of the VNTR in some genes [30,34-43].…”
Section: Introductionmentioning
“…Sp transcription factors are known inducers of human CYB5A expression, so it is possible that this VNTR has functional relevance. Promoter VNTRs have been shown to affect the expression of several human genes, and VNTRs in the canine DRD4 gene have been associated with behavioral phenotypes in German Shepherds . Although we found no association between these VNTRs and sulfonamide hypersensitivity in the dogs in this study, the functional consequences of these VNTRs merit additional study.…”
Section: Discussioncontrasting
“…Although it is difficult to accurately predict the regulatory domains for a particular gene other than the proximal promoter (often 0.5 to 1 kb upstream of the transcriptional start site), our group and others have demonstrated important domains for gene regulation can reside in both the most evolutionary conserved regions (ECRs) which are non-coding [10][12] and the highly polymorphic and often rapidly evolving variable number tandem repeats (VNTRs) [13][19]. In both cases the ECR or VNTR can be tens of thousands of bases from the major transcriptional start of a gene [20].…”
Section: Introductionmentioning