Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites.
Malaria parasites use antigenic variation to avoid immune clearance and increase the duration of infection in the human host. Variation at the surface of P. falciparum-infected erythrocytes is mediated by the differential control of a family of surface antigens encoded by var genes. Switching of var gene expression occurs in situ, mostly from telomere-associated loci, without detectable DNA alterations, suggesting that it is controlled by chromatin structure. We have identified chromatin modifications at telomeres that spread far into telomere-proximal regions, including var gene loci (>50 kb). One type of modification is mediated by a protein homologous to yeast Sir2 called PfSir2, which forms a chromosomal gradient of heterochromatin structure and histone hypoacetylation. Upon activation of a specific telomere-associated var gene, PfSir2 is removed from the promoter region and acetylation of histone occurs. Our data demonstrate that mutually exclusive transcription of var genes is linked to the dynamic remodeling of chromatin.
Freitas-Junior
Lucio H
LH
Institut Pasteur, Biology of Host-Parasite Interactions Unit-CNRS URA2581, 25, rue du Dr. Roux, 75724 Paris, France.
Hernandez-Rivas
Rosaura
R
Ralph
Stuart A
SA
Montiel-Condado
Dvorak
D
Ruvalcaba-Salazar
Omar K
OK
Rojas-Meza
Ana Paola
AP
Mâncio-Silva
Liliana
L
Leal-Silvestre
Ricardo J
RJ
Gontijo
Alisson Marques
AM
Shorte
Spencer
S
Scherf
Artur
A
D000818:Animals; D000940:Antigenic Variation / Q000235:genetics*; D002466:Cell Nucleolus / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D020868:Gene Silencing; D017125:Genes, Protozoan / Q000235:genetics; D006570:Heterochromatin / Q000235:genetics*; D006655:Histone Deacetylases / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D016253:Microscopy, Immunoelectron; D010963:Plasmodium falciparum / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics; D016615:Telomere / Q000235:genetics
D006570:Heterochromatin; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases