恶性疟原虫PfRUVBL蛋白结合于TARE区,var基因启动子位于亚端粒区。

IF 2.7 4区 医学 Q3 IMMUNOLOGY Pathogens and disease Pub Date : 2022-05-31 DOI:10.1093/femspd/ftac018
H. Saxena, Ashish Gupta
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引用次数: 2

摘要

为了生存和建立感染,疟原虫采用各种策略来逃避宿主的免疫反应。Var基因家族共有60个基因,在被感染的红细胞膜上表达寄生虫特异性蛋白PfEMP1,这是一种可变的表面抗原,通过不断切换PfEMP1的变体,帮助寄生虫在红细胞内发育周期中避免宿主免疫系统的检测和破坏。虽然染色质修饰被认为是调控这些变异基因单等位基因表达的一个突出现象,但指导这些修饰的精确组蛋白编码和分子参与者和机制尚未深入揭示。在这项研究中,我们对恶性疟原虫的RUVBL蛋白进行了功能表征,发现PfMYST(一种必需赖氨酸乙酰转移酶)和PfRUVBL蛋白复合物占据了疟原虫环期的TARE区和var基因启动子。此外,我们已经证明PfMYST/PfRUVBL复合物与核心组蛋白H3和H4相互作用。总的来说,本研究的发现通过确定表观遗传调节因子PfMYST和PfRUVBL在调节疟疾寄生虫var基因单等位基因表达中的潜在作用,增加了一层。
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P. falciparum PfRUVBL proteins binds at TARE region and var gene promoter located in subtelomeric region.
In order to survive and establish infection, Plasmodium parasite employ various strategies to evade host immune response. Var genes family, a repertoire of 60 genes, express parasite-specific protein PfEMP1, a variable surface antigen, on the membrane of infected erythrocyte, and by continuously switching the variants of PfEMP1, helps the parasite to avoid detection and destruction by host immune system during intra-erythrocytic developmental cycle. Although chromatin modifications are recognized to be a prominent phenomenon in regulation of mono-allelic expression of these var genes, however the precise histone codes and molecular players & mechanisms guiding these modifications are yet to be unravelled in depth. In this study, we have functionally characterized RUVBL proteins of P. falciparum and shown that PfMYST (an essential lysine acetyl transferase) and PfRUVBL protein complex occupy the TARE region and var gene promoter in ring stage of the parasite. Further we have demonstrated that PfMYST/PfRUVBL complex interact with core histone, H3 & H4. Overall the findings of this study adds a layer by identifying the potential role of epigenetic regulators, PfMYST & PfRUVBL in regulation of monoallelic expression of var genes in malaria parasite.
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来源期刊
Pathogens and disease
Pathogens and disease IMMUNOLOGY-INFECTIOUS DISEASES
CiteScore
7.40
自引率
3.00%
发文量
44
期刊介绍: Pathogens and Disease publishes outstanding primary research on hypothesis- and discovery-driven studies on pathogens, host-pathogen interactions, host response to infection and their molecular and cellular correlates. It covers all pathogens – eukaryotes, prokaryotes, and viruses – and includes zoonotic pathogens and experimental translational applications.
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