title: Mono-allelic VSG expression by RNA polymerase I in Trypanosoma brucei: expression site control from both ends?
abstract: Trypanosoma brucei is a vector borne, lethal protistan parasite of humans and livestock in sub-Saharan Africa. Antigenic variation of its cell surface coat enables the parasite to evade adaptive immune responses and to live freely in the blood of its mammalian hosts. The coat consists of ten million copies of variant surface glycoprotein (VSG) that is expressed from a single VSG gene, drawn from a large repertoire and located near the telomere at one of fifteen so-called bloodstream expression sites (BESs). Thus, antigenic variation is achieved by switching to the expression of a different VSG gene. A BES is a tandem array of expression site-associated genes and a terminal VSG gene. It is polycistronically transcribed by a multifunctional RNA polymerase I (RNAPI) from a short promoter that is located 45-60 kb upstream of the VSG gene. The mechanism(s) restricting VSG expression to a single BES are not well understood. There is convincing evidence that epigenetic silencing and transcription attenuation play important roles. Furthermore, recent data indicated that there is regulation at the level of transcription initiation and that, surprisingly, the VSG mRNA appears to have a role in restricting VSG expression to a single gene. Here, we review BES expression regulation and propose a model in which telomere-directed, epigenetic BES silencing is opposed by BES promoter-directed, activated RNAPI transcription.
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, 400 Farmington Avenue, Farmington, CT 06030-6403, USA. Electronic address: gunzl@uchc.edu.
authors.forename: Arthur
authors.initials: A
authors.lastname: Günzl
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, 400 Farmington Avenue, Farmington, CT 06030-6403, USA.
authors.forename: Justin K
authors.initials: JK
authors.lastname: Kirkham
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, 400 Farmington Avenue, Farmington, CT 06030-6403, USA.
authors.forename: Tu N
authors.initials: TN
authors.lastname: Nguyen
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, 400 Farmington Avenue, Farmington, CT 06030-6403, USA.
authors.forename: Nitika
authors.initials: N
authors.lastname: Badjatia
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, 400 Farmington Avenue, Farmington, CT 06030-6403, USA.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Park
mesh_terms: D000483:Alleles; D022981:Allelic Imbalance; D005786:Gene Expression Regulation; D020868:Gene Silencing; D017125:Genes, Protozoan; D011401:Promoter Regions, Genetic; D012318:RNA Polymerase I / Q000502:physiology*; D016615:Telomere / Q000235:genetics; D024363:Transcription Initiation Site; D014346:Trypanosoma brucei brucei / Q000235:genetics*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics*
chemical_list: D014643:Variant Surface Glycoproteins, Trypanosoma; D012318:RNA Polymerase I
keywords: Mono-allelic gene expression; RNA polymerase I; Telomeric silencing; Trypanosome