title: Plasmodium falciparum: epigenetic control of var gene regulation and disease.
abstract: 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.
authors.affiliation: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India.
authors.forename: Abhijit S
authors.initials: AS
authors.lastname: Deshmukh
authors.forename: Sandeep
authors.initials: S
authors.lastname: Srivastava
authors.forename: Suman Kumar
authors.initials: SK
authors.lastname: Dhar
mesh_terms: D000107:Acetylation; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004351:Drug Resistance / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006657:Histones / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D010641:Phenotype; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D011499:Protein Processing, Post-Translational; D015800:Protozoan Proteins / Q000235:genetics*; D014774:Virulence / Q000235:genetics
chemical_list: D000962:Antimalarials; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D051548:Histone Acetyltransferases