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Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor
Cell Host & Microbe ( IF 30.3 ) Pub Date : 2017-06-14 , DOI: 10.1016/j.chom.2017.05.006
Joana Mendonca Santos , Gabrielle Josling , Philipp Ross , Preeti Joshi , Lindsey Orchard , Tracey Campbell , Ariel Schieler , Ileana M. Cristea , Manuel Llinás

Obligate intracellular parasites must efficiently invade host cells in order to mature and be transmitted. For the malaria parasite Plasmodium falciparum, invasion of host red blood cells (RBCs) is essential. Here we describe a parasite-specific transcription factor PfAP2-I, belonging to the Apicomplexan AP2 (ApiAP2) family, that is responsible for regulating the expression of genes involved in RBC invasion. Our genome-wide analysis by ChIP-seq shows that PfAP2-I interacts with a specific DNA motif in the promoters of target genes. Although PfAP2-I contains three AP2 DNA-binding domains, only one is required for binding of the target genes during blood stage development. Furthermore, we find that PfAP2-I associates with several chromatin-associated proteins, including the Plasmodium bromodomain protein PfBDP1 and that complex formation is associated with transcriptional regulation. As a key regulator of red blood cell invasion, PfAP2-I represents a potential new antimalarial therapeutic target.



中文翻译:

PfAP2-I转录因子协调疟疾寄生虫对红细胞的入侵。

专性的细胞内寄生虫必须有效地侵入宿主细胞才能成熟并被传播。对于疟原虫恶性疟原虫,宿主红细胞(RBC)的入侵至关重要。在这里,我们描述了一种寄生虫特异性转录因子PfAP2-I,属于Apicomplexan AP2(ApiAP2)家族,该因子负责调节参与RBC侵袭的基因的表达。我们通过ChIP-seq进行的全基因组分析表明,PfAP2-I与靶基因启动子中的特定DNA图案相互作用。尽管PfAP2-I包含三个AP2 DNA结合结构域,但在血液发育过程中只需要一个结合靶基因即可。此外,我们发现PfAP2-I与几种与染色质相关的蛋白相关联,包括疟原虫溴结构域蛋白PfBDP1,并且复合物的形成与转录调控相关。作为红细胞入侵的关键调节剂,PfAP2-I代表了潜在的新抗疟治疗靶标。

更新日期:2017-06-14
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