Identification of nuclear proteins that interact differentially with Plasmodium falciparum var gene promoters
Identification of nuclear proteins that interact differentially with Plasmodium falciparum var gene promoters
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DOI：
10.1046/j.1365-2958.2003.03528.x
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发表时间：
2003-06-01
影响因子：
3.6
通讯作者：
Beck, HP
中科院分区：
文献类型：
--
作者：
Voss, TS;Kaestli, M;Beck, HP
恶性疟原虫毒力因子PfEMP 1负责疟疾中受感染红细胞的抗原变异和细胞粘附。每个寄生虫基因组大约有50个var基因编码这种高度多态性的表面蛋白。我们最近发现，染色体中央和亚端粒变异基因是由不同的启动子控制。在这里，我们报告，位于不同的染色体区域的var基因的转录抑制发生不同的机制。亚端粒区var基因的转录比染色体中心var基因的转录早4-8小时受到抑制。这两个阻遏事件与两个不同的核蛋白特异性结合保守序列基序SPE 1和CPE，存在于各自的启动子中的转移表达相一致。此外，一个重复的和高度保守的亚端粒变异启动子元件（SPE 2）相互作用的核因子专门在S期表达。瞬时转染的启动子分析表明，这些相互作用直接参与了var基因的抑制和沉默，并确定了与var基因的转录激活有关的区域。
The Plasmodium falciparum virulence factor PfEMP1 is responsible for both antigenic variation and cytoadherence of infected erythrocytes in malaria. Approximately 50 var genes per parasite genome code for this highly polymorphic surface protein. We showed recently that chromosome-central and subtelomeric var genes are controlled by different promoters. Here, we report that transcriptional repression of var genes located in different chromosomal regions occurs by different mechanisms. Subtelomeric var gene transcription is repressed 4-8 h before that of chromosome-central var genes. Both repression events coincide with the shifted expression of two distinct nuclear proteins binding specifically to conserved sequence motifs, SPE1 and CPE , present in the respective promoter. Furthermore, a reiterated and highly conserved subtelomeric var promoter element (SPE2 ) interacts with a nuclear factor exclusively expressed during S-phase. Promoter analysis by transient transfection suggested direct involvement of these interactions in var gene repression and silencing, and identified regions implicated in transcriptional activation of var genes.