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Influence of a critical single nucleotide polymorphism on nuclear receptor PXR-promoter function

机译:临界单核苷酸多态性对核受体PXR-启动子功能的影响

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The Pregnane and Xenobiotic Receptor (PXR; NR1I2) is a ligand-modulated transcription factor that belongs to the nuclear receptor superfamily. It is expressed at higher levels primarily in liver and intestine as compared to the levels in several other organs. It is activated by a broad spectrum of xenobiotics and endobiotics. The primary function of PXR is to regulate the expression of drug metabolizing enzymes and transporters and prevent the accumulation of toxic chemicals in the body, thereby maintaining body's homeostasis. In this study, we identified a C/T single nucleotide polymorphism at position -831 from the transcriptional start site of the PXR gene promoter and examined the functional significance of this variant using both the luciferase reporter gene assays and electrophoretic mobility shift assays (EMSA). Transient transfection experiments showed that the T-allele was associated with significantly greater transcriptional activity than the C-allele of SNP rs3814055. These results indicate that the -831C/T polymorphism has a direct effect on transcriptional regulation of PXR gene. This allelic variation may be a potential genetic marker that can help identify individuals at higher risk for Inflammatory Bowel Disease (IBD).
机译:妊娠和异丙酸受体(PXR; NR1I2)是属于核受体超家族的配体调节转录因子。与若干其他器官的水平相比,它在肝脏和肠中的较高水平表达。它由广谱激活的异卵和生物生物学激活。 PXR的主要功能是调节药物代谢酶和转运蛋白的表达,并防止体内毒性化学品的积累,从而保持身体的稳态。在该研究中,我们从PXR基因启动子的转录开始部位鉴定了在-831位的C / T单核苷酸多态性,并使用荧光素酶报告基因测定和电泳迁移率移位测定(EMSA)检查该变体的功能意义。瞬时转染实验表明,T-Allele与SNP RS3814055的C-等位基因有关的转录活性明显更大。这些结果表明-831C / T多态性对PXR基因的转录调节直接影响。这种等位基因变异可以是潜在的遗传标记,可以有助于识别炎症性肠病(IBD)较高风险的个体。

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