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Recognition of NFATp/AP-1 composite elements within genes induced upon the activation of immune cells.

机译:免疫细胞激活后诱导的基因中NFATp / AP-1复合元素的识别。

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摘要

Composite elements are regulatory modules of promoters or enhancers that consist of binding sites of two different but synergizing transcription factors. A well-studied example is nuclear factors of activated T-cell (NFAT) sites which are composite elements of a NFATp/c and an activating protein 1 (AP-1) binding site. We have developed a computational approach to identify potential NFAT target genes which (a) comprises an improved method to scan for individual NFAT composite elements; (b) considers positional effects relative to transcription start sites; and (c) involves cluster analysis of potential NFAT composite elements. All three steps progressively helpX?ed to discriminate T-cell-specific promoter sequences against other functional regions (coding and intronic sequences) of the same genes, against promoters of muscle-specific genes or against random sequences. Using this approach, we identified potential NFAT composite elements in promoters of cytokine genes and their receptors as well as in promoters of genes for AP-1 family members, Ca2+-binding proteins and some other components of the regulatory network operating in activated T-cells and other immune cells. The method developed can be adapted to characterize and identify other composite elements as well. The program for recognition NFAT composite elements is available through the World Wide Web (http://compel.bionet.nsc.ru/FunSite/CompelScan. html and http://transfac.gbf.de/dbsearch/funsitep/s _comp.html). Copyright 1999 Academic Press.
机译:复合元件是启动子或增强子的调节模块,其由两个不同但协同的转录因子的结合位点组成。一个经过充分研究的例子是活化T细胞(NFAT)位点的核因子,它是NFATp / c和活化蛋白1(AP-1)结合位点的复合元素。我们已经开发出一种计算方法来识别潜在的NFAT靶基因,其中(a)包括一种用于扫描单个NFAT复合元素的改进方法; (b)考虑相对于转录起始位点的位置影响; (c)涉及潜在的NFAT复合元素的聚类分析。所有这三个步骤逐渐有助于区分T细胞特异性启动子序列与同一基因的其他功能区(编码和内含子序列),肌肉特异性基因的启动子或随机序列。使用这种方法,我们在细胞因子基因及其受体的启动子以及AP-1家族成员,Ca2 +结合蛋白和在激活的T细胞中运作的调节网络的其他某些部分的基因的启动子中鉴定出了潜在的NFAT复合元素。和其他免疫细胞。开发的方法也可以适用于表征和识别其他复合元素。可通过万维网(http://compel.bionet.nsc.ru/FunSite/CompelScan.html和http://transfac.gbf.de/dbsearch/funsitep/s _comp获得NFAT复合元素识别程序)。 html)。版权所有1999,学术出版社。

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