Heterochromatin Silencing and Locus Repositioning Linked to Regulation of Virulence Genes in Plasmodium falciparum

The malaria parasite Plasmodium falciparum undergoes antigenic variation to evade host immune responses through switching expression of variant surface proteins encoded by the var gene family. We demonstrate that both a subtelomeric transgene and var genes are subject to reversible gene silencing. V...

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Bibliographic Details
Published in:Cell 2005-04, Vol.121 (1), p.13-24
Main Authors: Duraisingh, Manoj T., Voss, Till S., Marty, Allison J., Duffy, Michael F., Good, Robert T., Thompson, Jennifer K., Freitas-Junior, Lucio H., Scherf, Artur, Crabb, Brendan S., Cowman, Alan F.
Format: Article
Language:English
Subjects:
Animals
Antigenic Variation - genetics
Antigenic Variation - immunology
Cell Compartmentation - genetics
Cell Compartmentation - immunology
Cell Nucleus - genetics
Cell Nucleus - immunology
Chromatin Assembly and Disassembly - genetics
Chromosomes - genetics
Chromosomes - immunology
Gene Silencing - immunology
Genes, Protozoan - genetics
Genes, Protozoan - immunology
Heterochromatin - genetics
Heterochromatin - immunology
Humans
In Situ Hybridization, Fluorescence
Malaria, Falciparum - genetics
Malaria, Falciparum - parasitology
Microarray Analysis
Plasmids - genetics
Plasmids - immunology
Plasmodium falciparum
Plasmodium falciparum - genetics
Plasmodium falciparum - immunology
Plasmodium falciparum - pathogenicity
Telomere - genetics
Tetrahydrofolate Dehydrogenase - genetics
Virulence - genetics
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Description
Summary:The malaria parasite Plasmodium falciparum undergoes antigenic variation to evade host immune responses through switching expression of variant surface proteins encoded by the var gene family. We demonstrate that both a subtelomeric transgene and var genes are subject to reversible gene silencing. Var gene silencing involves the SIR complex as gene disruption of PfSIR2 results in activation of this gene family. We also demonstrate that perinuclear gene activation involves chromatin alterations and repositioning into a location that may be permissive for transcription. Together, this implies that locus repositioning and heterochromatic silencing play important roles in the epigenetic regulation of virulence genes in P. falciparum.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2005.01.036