Santos Joana Mendonca, Josling Gabrielle, Ross Philipp, Joshi Preeti, Orchard Lindsey, Campbell Tracey, Schieler Ariel, Cristea Ileana M, Llinás Manuel
Department of Biochemistry and Molecular Biology and Huck Center for Malaria Research, Pennsylvania State University, State College, PA 16802, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Department of Biochemistry and Molecular Biology and Huck Center for Malaria Research, Pennsylvania State University, State College, PA 16802, USA.
Cell Host Microbe. 2017 Jun 14;21(6):731-741.e10. doi: 10.1016/j.chom.2017.05.006.
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.
专性细胞内寄生虫必须有效地侵入宿主细胞才能成熟并传播。对于疟原虫恶性疟原虫而言，侵入宿主红细胞（RBC）至关重要。在此，我们描述了一种属于顶复门AP2（ApiAP2）家族的寄生虫特异性转录因子PfAP2-I，它负责调控参与红细胞侵入的基因的表达。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基序相互作用。尽管PfAP2-I包含三个AP2 DNA结合结构域，但在血液阶段发育过程中，靶基因的结合仅需要其中一个结构域。此外，我们发现PfAP2-I与几种染色质相关蛋白相关联，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。作为红细胞侵入的关键调节因子，PfAP2-I代表了一个潜在的新型抗疟治疗靶点。
