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首页> 外文期刊>Genes, brain, and behavior >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.
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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.

机译：DRD4基因5'区域中可变数目的串联重复序列的等位基因特异性转录活性在人类神经元细胞中具有刺激特异性。

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摘要

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.
机译：多巴胺受体D4（DRD4）基因包括几个可变数目的串联重复基因座，已被认为可调节DRD4基因表达模式。先前的研究表明，串联重复序列的两个最常见变体（每个重复单元120 bp）位于人类细胞系中与DRD4启动子相邻的5'区域中，具有不同的基础活性。在这种交流中，我们进一步表征了该多态性重复序列在体外引起组织，等位基因和刺激特异性转录活性的能力。将DRD4 5'串联重复序列的短和长变体克隆到含有SV40启动子的荧光素酶报道基因构建体中。将萤光素酶构建体与两种普遍表达的人类转录因子（TF），CCCTC结合因子（CTCF）和上游刺激因子2（USF2）的表达载体共转染到人类细胞系和新生大鼠皮层的原代培养物中，并测量萤光素酶活性。这些TF的过度表达导致萤光素酶构建体的细胞和等位基因特异性转录活性不同。我们的实验结果表明，该串联重复序列在DRD4基因5'启动子中的变异体将根据激活的信号途径，以细胞类型特异性的方式指导差异报告基因的转录活性。

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