title: Antigenic variation in African trypanosomes: the importance of chromosomal and nuclear context in VSG expression control.
abstract: African trypanosomes are lethal human and animal parasites that use antigenic variation for evasion of host adaptive immunity. To facilitate antigenic variation, trypanosomes dedicate approximately one third of their nuclear genome, including many minichromosomes, and possibly all sub-telomeres, to variant surface glycoprotein (VSG) genes and associated sequences. Antigenic variation requires transcription of a single VSG by RNA polymerase I (Pol-I), with silencing of other VSGs, and periodic switching of the expressed gene, typically via DNA recombination with duplicative translocation of a new VSG to the active site. Thus, telomeric location, epigenetic controls and monoallelic transcription by Pol-I at an extranucleolar site are prominent features of VSGs and their expression, with telomeres, chromatin structure and nuclear organization all making vitally important contributions to monoallelic VSG expression control and switching. We discuss VSG transcription, recombination and replication control within this chromosomal and sub-nuclear context.
authors.affiliation: Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Glover
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hutchinson
authors.forename: Sam
authors.initials: S
authors.lastname: Alsford
authors.forename: Richard
authors.initials: R
authors.lastname: McCulloch
authors.forename: Mark C
authors.initials: MC
authors.lastname: Field
authors.forename: David
authors.initials: D
authors.lastname: Horn
mesh_terms: D000940:Antigenic Variation / Q000235:genetics* / Q000276:immunology; D002843:Chromatin / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D006801:Humans; D012318:RNA Polymerase I / Q000378:metabolism; D011995:Recombination, Genetic; D016615:Telomere / Q000235:genetics; D014158:Transcription, Genetic; D014347:Trypanosoma brucei gambiense / Q000235:genetics* / Q000276:immunology; D014353:Trypanosomiasis, African / Q000276:immunology*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics* / Q000276:immunology*
chemical_list: D002843:Chromatin; D014643:Variant Surface Glycoproteins, Trypanosoma; D012318:RNA Polymerase I
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