title: Mechanisms underlying mutually exclusive expression of virulence genes by malaria parasites.
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.
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Box 62, New York, New York 10021, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Dzikowski
authors.forename: Felomena
authors.initials: F
authors.lastname: Li
authors.forename: Borko
authors.initials: B
authors.lastname: Amulic
authors.forename: Andrew
authors.initials: A
authors.lastname: Eisberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Frank
authors.forename: Suchit
authors.initials: S
authors.lastname: Patel
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wellems
authors.forename: Kirk W
authors.initials: KW
authors.lastname: Deitsch
mesh_terms: 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
chemical_list: D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum