Transcription factor AP2-Sp and its target genes in malarial sporozoites
Transcription factor AP2-Sp and its target genes in malarial sporozoites
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DOI：
10.1111/j.1365-2958.2009.07005.x
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发表时间：
2010-02-01
影响因子：
3.6
通讯作者：
Kaneko, Izumi
中科院分区：
文献类型：
--
作者：
Yuda, Masao;Iwanaga, Shiroh;Kaneko, Izumi
疟原虫子孢子是感染肝脏的阶段，在这一阶段表达的基因是疫苗开发的潜在靶点。在这里，我们表明，在这个阶段的特定基因表达的AP 2相关的转录因子，指定AP 2-SP（APETALA 2在子孢子），这是从晚期卵囊的唾液腺子孢子表达。AP 2-Sp基因的破坏不影响寄生虫在红细胞中的复制，但导致子孢子形成的损失。电泳迁移率变动分析表明，DNA结合域的AP 2-SP识别特定的八个碱基序列，开始与TGCATG，这是目前在近端启动子区的所有已知的子孢子特异性基因。启动子分析表明，这些序列作为顺式作用元件，是子孢子特异性基因的表达与不同的表达谱的关键。在表达内源性AP 2-O（动合子中的APETALA 2）但其AP 2结构域与AP 2-Sp结构域交换的转基因寄生虫中，AP 2-Sp的几个靶基因在动合子阶段被诱导。这些结果表明，AP 2-Sp是一个主要的转录因子，调节基因表达的子孢子阶段。
P>The malarial sporozoite is the stage that infects the liver, and genes expressed in this stage are potential targets for vaccine development. Here, we demonstrate that specific gene expression in this stage is regulated by an AP2-related transcription factor, designated AP2-Sp (APETALA2 in sporozoites), that is expressed from the late oocyst to the salivary gland sporozoite. Disruption of the AP2-Sp gene did not affect parasite replication in the erythrocyte but resulted in loss of sporozoite formation. The electrophoretic mobility-shift assay showed that the DNA-binding domain of AP2-Sp recognizes specific eight-base sequences, beginning with TGCATG, which are present in the proximal promoter region of all known sporozoite-specific genes. Promoter assays demonstrated that these sequences act as cis-acting elements and are critical for the expression of sporozoite-specific genes with different expression profiles. In transgenic parasites that express endogenous AP2-O (APETALA2 in ookinetes), but whose AP2 domain had been swapped with that of AP2-Sp, several target genes of AP2-Sp were induced in the ookinete stage. These results indicate that AP2-Sp is a major transcription factor that regulates gene expression in the sporozoite stage.