Medicine (Northwest Academic Centre) - Research Publications

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Author: Cowman, Alan × Author: Duffy, Michael × End date: 2005 × Start date: 2001 × Type: Journal Article ×

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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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    Transcription of multiple var genes by individual, trophozoite-stage Plasmodium falciparum cells expressing a chondroitin sulphate A binding phenotype
    Duffy, MF ; Brown, GV ; Basuki, W ; Krejany, EO ; Noviyanti, R ; Cowman, AF ; Reeder, JC (WILEY, 2002-03)
    In this study, we detected multiple var gene transcripts within single, mature trophozoite-infected red blood cells (iRBCs) bound to chondroitin sulphate A (CSA). Several of the var detected had previously been demonstrated to encode Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) variants with domains that mediated iRBC adhesion to receptors other than CSA. Parasites expressing the CSA-adherent phenotype transcribed far more of one var than of all others, but this gene was different from the two other var previously purported to encode adhesion to CSA. Previous work suggesting that only single var are transcribed by mature trophozoites needs re-examination in the light of these data from single, infected cells.