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首页> 外文期刊>Cytokine >Functional analysis of linker-scan mutants spanning the -376, -308, -244, and -238 polymorphic sites of the TNF-alpha promoter.
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Functional analysis of linker-scan mutants spanning the -376, -308, -244, and -238 polymorphic sites of the TNF-alpha promoter.

机译：跨越TNF-α启动子的-376，-308，-244和-238多态性位点的接头扫描突变体的功能分析。

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摘要

Tumor necrosis factor alpha (TNF-alpha) promoter polymorphisms have been linked to a large number of diseases but studies examining the possible direct functional effects of these polymorphisms have been contradictory. Previous studies compared TNF-alpha promoter constructs containing single nucleotide changes. We have now made a series of mutant constructs in which regions of the TNF-alpha promoter containing suspected functional single nucleotide polymorphisms, including -376, -308, -244 and -238, were replaced by a 10 bp linker scan sequence. These constructs were transiently transfected into the T cell line Jurkat, the B cell line Raji, and the monocytic cell line U937, and tested for basal and induced transcriptional activity. Mutant constructs covering both the -308 and -376 polymorphisms showed no significant differences in either basal or induced transcriptional activity. Constructs covering the -244/-238 region showed a small increase in basal activity in the U937 cell line. These results indicate (i) that the -308 and -376 regions are of no functional relevance for TNF-alpha promoter transcription, and (ii) that the -244/-238 region does not influence transcription in some cell lines but may have some role in transcription in others. Copyright 2001 Academic Press.
机译：肿瘤坏死因子α（TNF-α）启动子多态性已与许多疾病相关联，但研究检查这些多态性可能的直接功能作用的研究却是矛盾的。先前的研究比较了包含单个核苷酸变化的TNF-α启动子构建体。现在我们已经制成了一系列突变体构建体，其中包含可疑功能性单核苷酸多态性（包括-376，-308，-244和-238）的TNF-α启动子区域被10 bp接头扫描序列取代。将这些构建体瞬时转染到T细胞系Jurkat，B细胞系Raji和单核细胞系U937中，并测试其基础和诱导的转录活性。覆盖-308和-376多态性的突变体构建体在基础或诱导的转录活性上均无显着差异。覆盖-244 / -238区的构建体在U937细胞系中显示出基础活性的小幅增加。这些结果表明（i）-308和-376区与TNF-α启动子转录没有功能相关性，并且（ii）-244 / -238区不影响某些细胞系的转录，但可能具有某些在他人转录中的作用。版权所有2001，学术出版社。

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