An ApiAP2 member regulates expression of clonally variant genes of the human malaria parasite Plasmodium falciparum.
An ApiAP2 member regulates expression of clonally variant genes of the human malaria parasite Plasmodium falciparum.
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DOI：
10.1038/s41598-017-12578-y
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发表时间：
2017-10-25
影响因子：
4.6
通讯作者：
Scherf A
中科院分区：
文献类型：
--
作者：
Martins RM;Macpherson CR;Claes A;Scheidig-Benatar C;Sakamoto H;Yam XY;Preiser P;Goel S;Wahlgren M;Sismeiro O;Coppée JY;Scherf A
多样性表面抗原表达是恶性疟原虫慢性感染和发病机制的关键。这种原生动物寄生虫表达不同的表面分子，这些分子由克隆变异基因家族编码，如var，rif和stevor。控制单个成员激活的分子机制仍然不清楚。为了研究初始转录激活过程中的分子事件，我们将重点放在一个被预测与var基因家族5′上游区域结合的顶复门ApiAP 2转录因子家族成员AP 2-exp（PF 3D7_1466400）上。存活的AP 2-exp突变体寄生虫依赖于表达不少于短截短的蛋白质，包括N-末端AP 2 DNA结合结构域。突变体寄生虫的RNA-seq分析揭示了由克隆变异基因家族编码的出口蛋白质子集的转录变化。RIFIN和STEVOR的上调在蛋白质水平上得到验证。此外，在被突变体感染的宿主细胞表面上观察到形态学改变。这项工作指出了一个复杂的调控网络的克隆变异基因家族中的一个子集的成员的转录是由相同的转录因子。此外，我们强调了非DNA结合AP 2结构域在功能基因调控中的重要性。
Variegated surface antigen expression is key to chronic infection and pathogenesis of the human malaria parasite Plasmodium falciparum. This protozoan parasite expresses distinct surface molecules that are encoded by clonally variant gene families such as var, rif and stevor. The molecular mechanisms governing activation of individual members remain ill-defined. To investigate the molecular events of the initial transcriptional activation process we focused on a member of the apicomplexan ApiAP2 transcription factor family predicted to bind to the 5′ upstream regions of the var gene family, AP2-exp (PF3D7_1466400). Viable AP2-exp mutant parasites rely on expressing no less than a short truncated protein including the N-terminal AP2 DNA-binding domain. RNA-seq analysis in mutant parasites revealed transcriptional changes in a subset of exported proteins encoded by clonally variant gene families. Upregulation of RIFINs and STEVORs was validated at the protein levels. In addition, morphological alterations were observed on the surface of the host cells infected by the mutants. This work points to a complex regulatory network of clonally variant gene families in which transcription of a subset of members is regulated by the same transcription factor. In addition, we highlight the importance of the non-DNA binding AP2 domain in functional gene regulation.
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影响因子：
4.6
作者：
Cobbold SA;Santos JM;Ochoa A;Perlman DH;Llinás M
通讯作者：
Llinás M
影响因子：
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Llinás M
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Dear, PH
影响因子：
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