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PfSET10, a Plasmodium falciparum methyltransferase, maintains the active var gene in a poised state during parasite

Jennifer C Volz1, Richard Bártfai, Michaela Petter

  • 1The Walter and Eliza Hall Institute for Medical Research, Melbourne, Victoria, Australia.

Cell Host & Microbe
|January 24, 2012
PubMed

Insights

A newly identified protein, PfSET10, is crucial for malaria parasite Plasmodium falciparum to evade the immune system. This protein maintains the expression of virulence genes, enabling antigenic variation in the parasite.

Area of Science:

  • Malariology
  • Epigenetics
  • Molecular Parasitology

Background:

  • Erythrocyte membrane protein 1 (PfEMP1) is a key virulence factor in Plasmodium falciparum malaria.
  • PfEMP1 mediates infected erythrocyte adhesion and pathogenesis.
  • Antigenic variation, achieved through mutually exclusive transcription of ~60 var genes, allows parasite immune evasion.

Purpose of the Study:

  • To identify proteins involved in maintaining active var gene expression.
  • To elucidate the role of such proteins in Plasmodium falciparum antigenic variation.

Main Methods:

  • Localization studies to identify PfSET10's cellular location.
  • Biochemical assays to determine PfSET10's enzymatic activity (histone methyltransferase).
  • Functional studies to assess PfSET10's requirement for var gene expression and parasite survival.

Main Results:

  • PfSET10 localizes to the perinuclear active var gene expression site.
  • PfSET10 is a histone 3 lysine 4 methyltransferase essential for maintaining active var genes.
  • PfSET10 is required for Plasmodium falciparum antigenic variation and epigenetic memory transmission.

Conclusions:

  • PfSET10 plays a critical role in epigenetic regulation of var genes.
  • This epigenetic mechanism ensures heritable transmission of virulence gene expression during parasite division.
  • PfSET10 is a potential target for malaria control strategies.

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