Deshmukh Abhijit S, Srivastava Sandeep, Dhar Suman Kumar
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India.
Subcell Biochem. 2013;61:659-82. doi: 10.1007/978-94-007-4525-4_28.
Plasmodium falciparum, one of the deadliest parasites on earth causes human malaria resulting one million deaths annually. Central to the parasite pathogenicity and morbidity is the switching of parasite virulence (var) gene expression causing host immune evasion. The regulation of Plasmodium var gene expression is poorly understood. The complex life cycle of Plasmodium and mutually exclusive expression pattern of var genes make this disease difficult to control. Recent studies have demonstrated the pivotal role of epigenetic mechanism for control of coordinated expression of var genes, important for various clinical manifestations of malaria. In this review, we discuss about different Plasmodium histones and their various modifications important for gene expression and gene repression.Contribution of epigenetic mechanism to understand the var gene expression is also highlighted. We also describe in details P. falciparum nuclear architecture including heterochromatin, euchromatin and telomeric regions and their importance in subtelomeric and centrally located var gene expression. Finally, we explore the possibility of using Histone Acetyl Transferase (HAT) and Histone Deacetylase (HDAC)inhibitors against multi-drug resistance malaria parasites to provide another line of treatment for malaria.
恶性疟原虫是地球上最致命的寄生虫之一，可导致人类疟疾，每年造成100万人死亡。寄生虫的致病性和发病率的核心在于寄生虫毒力（var）基因表达的转换，从而导致宿主免疫逃避。目前对疟原虫var基因表达的调控了解甚少。疟原虫复杂的生命周期以及var基因相互排斥的表达模式使得这种疾病难以控制。最近的研究表明，表观遗传机制在控制var基因的协调表达中起着关键作用，这对疟疾的各种临床表现很重要。在这篇综述中，我们讨论了不同的疟原虫组蛋白及其对基因表达和基因抑制重要的各种修饰。还强调了表观遗传机制对理解var基因表达的贡献。我们还详细描述了恶性疟原虫的核结构，包括异染色质、常染色质和端粒区域，以及它们在亚端粒和位于中心的var基因表达中的重要性。最后，我们探讨了使用组蛋白乙酰转移酶（HAT）和组蛋白去乙酰化酶（HDAC）抑制剂对抗多药耐药疟原虫以提供另一种疟疾治疗方法的可能性。
