VEX1 controls the allelic exclusion required for antigenic variation in trypanosomes

Lucy Glover, Sebastian Hutchinson, Sam Alsford, David Horn (Lead / Corresponding author)

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Abstract

Allelic exclusion underpins antigenic variation and immune evasion in African trypanosomes. These bloodstream parasites employ RNA polymerase-I (pol-I) to transcribe just one telomeric variant surface glycoprotein (VSG) gene at a time, producing superabundant and switchable VSG-coats. We identified trypanosome VSG-exclusion-1 (VEX1) using a genetic-screen for defects in telomere-exclusive expression. VEX1 was sequestered by the active VSG and silencing of other VSGs failed when VEX1 was either ectopically expressed or depleted, indicating positive and negative regulation, respectively. Positive regulation affected VSGs and non-telomeric pol-I transcribed genes while negative regulation primarily affected VSGs. Negative regulation by VEX1 also affected telomeric pol-I transcribed reporter constructs, but only when they contained blocks of sequence sharing homology with a pol-I transcribed locus. We conclude that restricted positive regulation due to VEX1 sequestration, combined with VEX1-dependent, possibly homology-dependent silencing, drives a 'winner-take-all' mechanism of allelic exclusion.
Original languageEnglish
Pages (from-to)7225-7230
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number26
Early online date25 May 2016
DOIs
Publication statusPublished - 28 Jun 2016

Keywords

  • epigenetic
  • monoallelic
  • silencing
  • telomere
  • Trypanosoma brucei

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    VSG expression in African trypanosomes: Gene silencing, cell cycle and developmental control

    Author: Hutchinson, S. J., 2016

    Supervisor: Horn, D. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

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