Mechanisms underlying mutually exclusive expression of virulence genes by malaria parasites.
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.
Dzikowski
Ron
R
Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Box 62, New York, New York 10021, USA.
Li
Felomena
F
Amulic
Borko
B
Eisberg
Andrew
A
Frank
Matthias
M
Patel
Suchit
S
Wellems
Thomas E
TE
Deitsch
Kirk W
KW
D000818:Animals; D020868:Gene Silencing; D017403:In Situ Hybridization; D016778:Malaria, Falciparum / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000235:genetics* / Q000472:pathogenicity; D011401:Promoter Regions, Genetic / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics*; D014774:Virulence / Q000235:genetics
D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum