Identification of nuclear proteins that interact differentially with Plasmodium falciparum var gene promoters.
The Plasmodium falciparum virulence factor PfEMP1 is responsible for both antigenic variation and cytoadherence of infected erythrocytes in malaria. Approximately 50 var genes per parasite genome code for this highly polymorphic surface protein. We showed recently that chromosome-central and subtelomeric var genes are controlled by different promoters. Here, we report that transcriptional repression of var genes located in different chromosomal regions occurs by different mechanisms. Subtelomeric var gene transcription is repressed 4-8 h before that of chromosome-central var genes. Both repression events coincide with the shifted expression of two distinct nuclear proteins binding specifically to conserved sequence motifs, SPE1 and CPE, present in the respective promoter. Furthermore, a reiterated and highly conserved subtelomeric var promoter element (SPE2) interacts with a nuclear factor exclusively expressed during S-phase. Promoter analysis by transient transfection suggested direct involvement of these interactions in var gene repression and silencing, and identified regions implicated in transcriptional activation of var genes.
Voss
Till S
TS
Swiss Tropical Institute, Department of Medical Parasitology and Infection Biology, Socinstrasse 57, 4051 Basel, Switzerland.
Kaestli
Mirjam
M
Vogel
Denise
D
Bopp
Selina
S
Beck
Hans-Peter
HP
D000818:Animals; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000235:genetics; D001483:Base Sequence; D002875:Chromosomes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D011401:Promoter Regions, Genetic; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D000953:Antigens, Protozoan; D004268:DNA-Binding Proteins; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum