title: Evidence that Plasmodium falciparum chromosome end clusters are cross-linked by protein and are the sites of both virulence gene silencing and activation.
abstract: The malaria parasite Plasmodium falciparum undergoes antigenic variation through allelic exclusion and variant expression of surface proteins encoded by the var gene family. Regulation of var genes is under epigenetic control and involves reversible silencing and activation that requires the physical repositioning of a var locus into a transcriptionally permissive zone of the nuclear periphery. P. falciparum chromosome ends appear to aggregate into large perinuclear clusters which house both subtelomeric and chromosome central var genes. In this study we further define the composition of telomeric clusters using fluorescent in situ hybridization, and provide evidence that chromosome end clusters are formed by cross-linking protein. In addition, we demonstrate that a subtelomeric reporter gene and a var gene remain within clusters regardless of their transcriptional status. Our findings support a model whereby a highly localized structure dedicated to the activation of a single var gene can be housed within a gene dense chromosome end cluster that is otherwise transcriptionally silent.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Marty
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Thompson
authors.forename: Michael F
authors.initials: MF
authors.lastname: Duffy
authors.forename: Till S
authors.initials: TS
authors.lastname: Voss
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics* / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics; D020868:Gene Silencing; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D015800:Protozoan Proteins