Mechanisms underlying mutually exclusive expression of virulence genes by malaria parasites

Ron Dzikowski, Felomena Li, Borko Amulic, Andrew Eisberg, Matthias Frank, Suchit Patel, Thomas E Wellems, Kirk W Deitsch

Research output: Contribution to journalArticle (Academic Journal)peer-review

99 Citations (Scopus)

Abstract

A fundamental yet poorly understood aspect of gene regulation in eukaryotic organisms is the mechanisms that control allelic exclusion and mutually exclusive gene expression. In the malaria parasite Plasmodium falciparum, this process regulates expression of the var gene family--a large, hypervariable repertoire of genes that are responsible for the ability of the parasite to evade the host immune system and for pathogenesis of the disease. A central problem in understanding this process concerns the mechanisms that limit expression to a single gene at a time. Here, we describe results that provide information on the mechanisms that control silencing and single gene expression and differentiate between several models that have recently been proposed. The results provide the first evidence, to our knowledge, supporting the existence of a postulated var-specific, subnuclear expression site and also reinforce the conclusion that var gene regulation is based on cooperative interactions between the two promoters of each var gene.

Original languageEnglish
Pages (from-to)959-65
Number of pages7
JournalEMBO Reports
Volume8
Issue number10
DOIs
Publication statusPublished - Oct 2007

Keywords

  • Animals
  • Gene Silencing
  • In Situ Hybridization
  • Malaria, Falciparum
  • Plasmodium falciparum
  • Promoter Regions, Genetic
  • Protozoan Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic
  • Virulence
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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