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首页> 外文期刊>Addiction biology >Cell-specific effects of variants of the 68-base pair tandem repeat on prodynorphin gene promoter activity.
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Cell-specific effects of variants of the 68-base pair tandem repeat on prodynorphin gene promoter activity.

机译：68个碱基对的串联重复序列的变体对前强啡肽基因启动子活性的细胞特异性作用。

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摘要

A polymorphic 68-bp tandem repeat has been identified within the promoter of the human prodynorphin (PDYN) gene. We found that this 68-bp repeat in the PDYN promoter occurs naturally up to five times. We studied the effect of the number of 68-bp repeats, and of a SNP (rs61761346) found within the repeat on PDYN gene promoter activity. Thirteen promoter forms, different naturally occurring combinations of repeats and the internal SNP, were cloned upstream of the luciferase reporter gene, transfected into human SK-N-SH, H69, or HEK293 cells. Cells were then stimulated with TPA or caffeine. We found cell-specific effects of the number of 68-bp repeats on the transcriptional activity of the PDYN promoter. In SK-N-SH and H69 cells, three or four repeats led to lower expression of luciferase than did one or two repeats. The opposite effect was found in HEK293 cells. The SNP also had an effect on PDYN gene expression in both SK-N-SH and H69 cells; promoter forms with the A allele had significantly higher expression than promoter forms with the G allele. These results further our understanding of the complex transcriptional regulation of the PDYN gene promoter.
机译：在人类前强啡肽（PDYN）基因的启动子内已鉴定出多态性68 bp的串联重复序列。我们发现PDYN启动子中的这个68 bp重复自然发生多达五次。我们研究了68 bp重复的数目以及在该重复物中发现的SNP（rs61761346）对PDYN基因启动子活性的影响。在萤光素酶报告基因的上游克隆了13种启动子形式，不同的天然重复序列和内部SNP组合，转染到人SK-N-SH，H69或HEK293细胞中。然后用TPA或咖啡因刺激细胞。我们发现68 bp重复数对PDYN启动子的转录活性的细胞特异性影响。在SK-N-SH和H69细胞中，三个或四个重复序列导致的荧光素酶表达低于一个或两个重复序列。在HEK293细胞中发现相反的作用。 SNP还对SK-N-SH和H69细胞中的PDYN基因表达有影响。具有A等位基因的启动子形式的表达明显高于具有G等位基因的启动子形式。这些结果使我们进一步了解了PDYN基因启动子的复杂转录调控。

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