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一个内含子多态性重复序列调节白细胞介素-1α基因的调控。

An intronic polymorphic repeat sequence modulates interleukin-1 alpha gene regulation.

作者信息

Bailly S, Israël N, Fay M, Gougerot-Pocidalo M A, Duff G W

机构信息

DBMS/BRCE-INSERM U244, CENG, Grenoble, France.

出版信息

Mol Immunol. 1996 Aug;33(11-12):999-1006. doi: 10.1016/s0161-5890(96)00042-9.

DOI:10.1016/s0161-5890(96)00042-9
PMID:8960124
Abstract

Recently, we characterized a polymorphism within IL-1 alpha intron 6 as a variable number of a 46 bp tandem repeat (ranging from 5 to 18 repeats). We now analyse whether this polymorphism could play a role in IL-1 alpha gene regulation. We have found that reporter gene expression driven by the IL-1 alpha promoter or a heterologous promoter was decreased by increasing numbers of the repeat sequence corresponding to the most frequent alleles seen in the human population. Furthermore, we showed that the transcription factor Sp1 can bind to the 46 bp sequence. Finally, we were unable to show a statistically-significant relation between in vitro IL-1 alpha production and the number of repeats although there was a clear trend towards an inverse relation. Taken together, these results are consistent with a negative regulatory role for IL-1 alpha intron 6 repeat sequence on IL-1 alpha basal gene transcription.

摘要

最近,我们将白细胞介素-1α(IL-1α)内含子6中的一种多态性特征化为46 bp串联重复序列的可变数量(范围为5至18个重复)。我们现在分析这种多态性是否可能在IL-1α基因调控中发挥作用。我们发现,由IL-1α启动子或异源启动子驱动的报告基因表达会随着对应于人群中最常见等位基因的重复序列数量增加而降低。此外,我们表明转录因子Sp1可以结合到46 bp序列上。最后,尽管存在明显的负相关趋势,但我们未能显示出体外IL-1α产生与重复序列数量之间具有统计学意义的关系。综上所述,这些结果与IL-1α内含子6重复序列对IL-1α基础基因转录的负调控作用一致。

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An intronic polymorphic repeat sequence modulates interleukin-1 alpha gene regulation.一个内含子多态性重复序列调节白细胞介素-1α基因的调控。
Mol Immunol. 1996 Aug;33(11-12):999-1006. doi: 10.1016/s0161-5890(96)00042-9.
2
Polymorphic tandem repeat region in interleukin-1 alpha intron 6.白细胞介素-1α基因内含子6中的多态性串联重复序列区域
Hum Genet. 1993 Mar;91(1):85-6. doi: 10.1007/BF00230231.
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Interleukin-1 alpha gene intron containing variable repeat region coding for the SP1 transcription factor recognition sequence is polymorphic.含编码SP1转录因子识别序列的可变重复区域的白细胞介素-1α基因内含子具有多态性。
Mol Carcinog. 1989;2(2):68-71. doi: 10.1002/mc.2940020204.
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Genetic polymorphism of human interleukin-1 alpha.人类白细胞介素-1α的基因多态性
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Absence of correlation between IL-1 alpha intron 6 polymorphism and rheumatoid arthritis.白细胞介素-1α基因内含子6多态性与类风湿性关节炎之间不存在相关性。
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Cloning and functional analysis of the allelic polymorphism in the transcription regulatory region of interleukin-1 alpha.
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Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro.白细胞介素-1受体拮抗剂(IL-1RA)等位基因2(IL1RN*2)的存在与体外白细胞介素-1β(IL-1β)产量增加相关。
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Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat.人类白细胞介素-1受体拮抗剂基因内含子2的多态性是由一个86碱基对串联重复序列的数目可变引起的。
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Molecular characterization and clinical use of a polymorphic tandem repeat in an intron of the human alanine:glyoxylate aminotransferase gene.人丙氨酸:乙醛酸转氨酶基因内含子中一个多态性串联重复序列的分子特征及临床应用
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A novel NF-kappa B/Rel site in intron 1 cooperates with proximal promoter elements to mediate TNF-alpha-induced transcription of the human polymeric Ig receptor.内含子1中一个新的核因子-κB/Rel位点与近端启动子元件协同作用,介导肿瘤坏死因子-α诱导的人多聚免疫球蛋白受体转录。
J Immunol. 2001 Dec 1;167(11):6412-20. doi: 10.4049/jimmunol.167.11.6412.

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