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恶性疟原虫基因组中调控元件的鉴定

Identification of regulatory elements in the Plasmodium falciparum genome.

作者信息

Militello Kevin T, Dodge Matthew, Bethke Lara, Wirth Dyann F

机构信息

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.

出版信息

Mol Biochem Parasitol. 2004 Mar;134(1):75-88. doi: 10.1016/j.molbiopara.2003.11.004.

DOI:10.1016/j.molbiopara.2003.11.004
PMID:14747145
Abstract

There is little information regarding regulatory sequences in the newly sequenced genome of the malaria parasite, Plasmodium falciparum. Thus, for the first time, a bioinformatic strategy was utilized to identify regulatory elements in this genome using the P. falciparum heat shock protein (hsp) gene family as a model system. Our analysis indicates that the P. falciparum hsp genes do not contain standard eukaryotic regulatory elements. However, a novel G-rich regulatory element named the G-box was identified upstream of several P. falciparum hsp genes and the P. yoelii yoelii, P. berghei, and P. vivax hsp86 genes. Remarkably, the Plasmodium sp. G-boxes were required for maximal reporter gene expression in transient transfection assays. The G-box is not homologous to known eukaryotic elements, and is the best-defined functional element elucidated from Plasmodium sp. Our analysis also revealed several other elements necessary for reporter gene expression including an upstream sequence element, the region surrounding the transcription start site, and the 5' and 3' untranslated regions. These data demonstrate that unique regulatory elements are conserved in the genomes of Plasmodium sp., and demonstrate the feasibility of bioinformatic approaches for their identification.

摘要

关于疟原虫恶性疟原虫新测序基因组中的调控序列,目前所知甚少。因此,首次利用生物信息学策略,以恶性疟原虫热休克蛋白(hsp)基因家族作为模型系统,来识别该基因组中的调控元件。我们的分析表明,恶性疟原虫的hsp基因不包含标准的真核生物调控元件。然而,在几个恶性疟原虫hsp基因以及约氏疟原虫、伯氏疟原虫和间日疟原虫的hsp86基因上游,发现了一种名为G盒的新型富含G的调控元件。值得注意的是,在瞬时转染实验中,疟原虫属的G盒是报告基因最大表达所必需的。G盒与已知的真核生物元件不同源,是从疟原虫属中阐明的定义最明确的功能元件。我们的分析还揭示了报告基因表达所需的其他几个元件,包括上游序列元件、转录起始位点周围的区域以及5'和3'非翻译区。这些数据表明,独特的调控元件在疟原虫属的基因组中是保守的,并证明了生物信息学方法识别它们的可行性。

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