VEX1 controls the allelic exclusion required for antigenic variation in trypanosomes.


Glover, L; Hutchinson, S; Alsford, S; Horn, D; (2016) VEX1 controls the allelic exclusion required for antigenic variation in trypanosomes. Proceedings of the National Academy of Sciences of the United States of America. ISSN 0027-8424 DOI: https://doi.org/10.1073/pnas.1600344113

[img]
Preview
Text - Published Version
License:

Download (1MB) | Preview
[img]
Preview
Text - Accepted Version
License:

Download (5MB) | Preview

Abstract

Allelic exclusion underpins antigenic variation and immune evasion in African trypanosomes. These bloodstream parasites use 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 nontelomeric pol-I-transcribed genes, whereas 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-takes-all" mechanism of allelic exclusion.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 27226299
Web of Science ID: 379033400069
URI: http://researchonline.lshtm.ac.uk/id/eprint/2550088

Statistics


Download activity - last 12 months
Downloads since deposit
30Downloads
77Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item