Antigenic variation in malaria:: in situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum
Antigenic variation in malaria:: in situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum
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DOI：
10.1093/emboj/17.18.5418
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发表时间：
1998-09-15
期刊：
影响因子：
11.4
通讯作者：
Lanzer, M
中科院分区：
文献类型：
--
作者：
Scherf, A;Hernandez-Rivas, R;Lanzer, M
恶性疟原虫var基因家族成员编码克隆性变异型粘附素，在热带疟疾的致病过程中发挥重要作用。在这里，我们使用选择性淘洗方案来产生具有CD36、ICAM-1和CsA定义的黏附表型的等基因恶性疟原虫群体，表达单一和不同的var基因变体。该技术为研究var基因的表达、调控和转换奠定了基础。研究发现，var基因发生了非原位转换。所有var基因变体的普遍转录似乎发生在环的早期阶段。然而，var基因在滋养体中的表达受到严格的调控，并通过沉默机制发挥作用。转录控制在表达特定粘附性表型的寄生虫中是相互排斥的。正如核连续分析所证明的那样，Lit原位var基因切换显然是在转录启动水平上调节的。我们的结果表明，var基因的调控涉及表观遗传机制(S)。
Members of the Plasmodium falciparum var gene family encode clonally variant adhesins, which play an important role in the pathogenicity of tropical malaria. Here we employ a selective panning protocol to generate isogenic P falciparum populations with defined adhesive phenotypes for CD36, ICAM-1 and CSA, expressing single and distinct var gene variants. This technique has established the framework for examining var gene expression, its regulation and switching. It was found that var gene switching occurs irt situ. Ubiquitous transcription of all var gene variants appears to occur in early ring stages. However, var gene expression is tightly regulated in trophozoites and is exerted through a silencing mechanism. Transcriptional control is mutually exclusive in parasites that express defined adhesive phenotypes. lit situ var gene switching is apparently mediated at the level of transcriptional initiation, as demonstrated by nuclear run-on analyses. Our results suggest that an epigenetic mechanism(s) is involved in var gene regulation.