Epigenetic memory at malaria virulence genes

Thanat Chookajorn*, Ron Dzikowski, Matthias Frank, Felomena Li, Alisha Z. Jiwani, Daniel L. Hartl, Kirk W. Deitsch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

186 Scopus citations

Abstract

During its red blood cell stage, the malaria parasite Plasmodium falciparum can switch its variant surface proteins (P. falciparum erythrocyte membrane protein 1) to evade the host immune response. The var gene family encodes P. falciparum erythrocyte membrane protein 1, different versions of which have unique binding specificities to various human endothelial surface molecules. Individual parasites each contain ≈60 var genes at various locations within their chromosomes; however, parasite isolates contain different complements of var genes, thus, the gene family is enormous with a virtually unlimited number of members. A single var gene is expressed by each parasite in a mutually exclusive manner. We report that control of var gene transcription and antigenic variation is associated with a chromatin memory that includes methylation of histone H3 at lysine K9 as an epigenetic mark. We also discuss how gene transcription memory may affect the mechanism of pathogenesis and immune evasion.

Original languageAmerican English
Pages (from-to)899-902
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number3
DOIs
StatePublished - 16 Jan 2007
Externally publishedYes

Keywords

  • Antigenic variation
  • Chromatin
  • Histone modification
  • Monoallelic expression

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