Scherf A, Hernandez-Rivas R, Buffet P, Bottius E, Benatar C, Pouvelle B, Gysin J, Lanzer M
Unité de Biologie des Interactions Hôte-Parasite, CNRS URA 1960, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
EMBO J. 1998 Sep 15;17(18):5418-26. doi: 10.1093/emboj/17.18.5418.
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 in 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. In 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.
恶性疟原虫var基因家族的成员编码克隆性可变黏附素,其在热带疟疾的致病性中起重要作用。在此,我们采用一种选择性淘选方案来生成具有针对CD36、ICAM - 1和CSA的特定黏附表型的同基因恶性疟原虫群体,这些群体表达单个且不同的var基因变体。该技术为研究var基因表达、其调控和转换建立了框架。研究发现var基因转换在原位发生。所有var基因变体的普遍转录似乎发生在早期环状体阶段。然而,var基因表达在滋养体中受到严格调控,并通过一种沉默机制发挥作用。在表达特定黏附表型的寄生虫中,转录控制是相互排斥的。如核延伸分析所示,原位var基因转换显然是在转录起始水平介导的。我们的结果表明一种表观遗传机制参与了var基因调控。