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Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei

Please always quote using this URN: urn:nbn:de:bvb:20-opus-119727
  • We have discovered a new mechanism of monoallelic gene expression that links antigenic variation, cell cycle, and development in the model parasite Trypanosoma brucei. African trypanosomes possess hundreds of variant surface glycoprotein (VSG) genes, but only one is expressed from a telomeric expression site (ES) at any given time. We found that the expression of a second VSG alone is sufficient to silence the active VSG gene and directionally attenuate the ES by disruptor of telomeric silencing-1B (DOT1B)-mediated histone methylation. ThreeWe have discovered a new mechanism of monoallelic gene expression that links antigenic variation, cell cycle, and development in the model parasite Trypanosoma brucei. African trypanosomes possess hundreds of variant surface glycoprotein (VSG) genes, but only one is expressed from a telomeric expression site (ES) at any given time. We found that the expression of a second VSG alone is sufficient to silence the active VSG gene and directionally attenuate the ES by disruptor of telomeric silencing-1B (DOT1B)-mediated histone methylation. Three conserved expression-site-associated genes (ESAGs) appear to serve as signal for ES attenuation. Their depletion causes G1-phase dormancy and reversible initiation of the slender-to-stumpy differentiation pathway. ES-attenuated slender bloodstream trypanosomes gain full developmental competence for transformation to the tsetse fly stage. This surprising connection between antigenic variation and developmental progression provides an unexpected point of attack against the deadly sleeping sickness.show moreshow less

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Metadaten
Author: Christopher Batram, Nivola G. Jones, Christian J. Janzen, Sebastian M. Markert, Markus Engstler
URN:urn:nbn:de:bvb:20-opus-119727
Document Type:Journal article
Faculties:Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):eLife
ISSN:2050-084X
Year of Completion:2014
Volume:3
Issue:e02324
Source:eLife 2014;3:e02324. DOI: 10.7554/eLife.02324
DOI:https://doi.org/10.7554/eLife.02324
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 579 Mikroorganismen, Pilze, Algen
Tag:Trypanosoma brucei; antigenic variation; cell biology; developmental reprogramming; expression site attenuation; genes and chromosomes; monoallelic expression; variant surface glycoprotein (VSG)
Release Date:2015/11/12
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung