Medicine (Northwest Academic Centre) - Research Publications

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2005 2
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Type: Journal Article × Subject: Infectious Diseases; Infectious Diseases × Author: Duffy, Michael ×

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    Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium faiciparum
    Duraisingh, MT ; Voss, TS ; Marty, AJ ; Duffy, MF ; Good, RT ; Thompson, JK ; Freitas-Junior, LH ; Scherf, A ; Crabb, BS ; Cowman, AF (CELL PRESS, 2005-04-08)
    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.
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    Broad analysis reveals a consistent pattern of var gene transcription in Plasmodium falciparum repeatedly selected for a defined adhesion phenotype
    Duffy, MF ; Byrne, TJ ; Elliott, SR ; Wilson, DW ; Rogerson, SJ ; Beeson, JG ; Noviyanti, R ; Brown, GV (WILEY, 2005-05)
    Transcription of the majority of the members of the Plasmodium falciparum var multigene family were analysed in two isolates by a quantitative approach. Both of these isolates had been repeatedly selected for adhesion to chondroitin sulphate A (CSA) and one had also been selected for adhesion to hyaluronic acid (HA). These adhesion phenotypes are expressed by many parasites isolated from placentae and are associated with malaria disease in pregnancy. Increased transcription of the var gene var2csa, or its homologue IT4 var4, was associated with the CSA and HA adhesion phenotypes in all parasites suggesting that it was the dominant, if not the only, var gene that encoded adhesion to CSA in these allogeneic isolates. Some var genes were consistently transcribed at higher levels than others regardless of expressed adhesion phenotypes suggesting a transcriptional hierarchy. Unspliced or partial transcripts were detected for most var genes tested. These atypical var gene transcripts may have implications for the regulation of var gene transcription.