title: Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites.
abstract: 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.
authors.affiliation: Institut Pasteur, Biology of Host-Parasite Interactions Unit-CNRS URA2581, 25, rue du Dr. Roux, 75724 Paris, France.
authors.forename: Lucio H
authors.initials: LH
authors.lastname: Freitas-Junior
authors.forename: Rosaura
authors.initials: R
authors.lastname: Hernandez-Rivas
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Ralph
authors.forename: Dvorak
authors.initials: D
authors.lastname: Montiel-Condado
authors.forename: Omar K
authors.initials: OK
authors.lastname: Ruvalcaba-Salazar
authors.forename: Ana Paola
authors.initials: AP
authors.lastname: Rojas-Meza
authors.forename: Liliana
authors.initials: L
authors.lastname: Mâncio-Silva
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Leal-Silvestre
authors.forename: Alisson Marques
authors.initials: AM
authors.lastname: Gontijo
authors.forename: Spencer
authors.initials: S
authors.lastname: Shorte
authors.forename: Artur
authors.initials: A
authors.lastname: Scherf
mesh_terms: 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
chemical_list: D006570:Heterochromatin; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases