Projects per year
Abstract
The largest gene families in eukaryotes are subject to allelic exclusion, but mechanisms underpinning single allele selection and inheritance remain unclear. Here, we describe a protein complex sustaining variant surface glycoprotein (VSG) allelic exclusion and antigenic variation in Trypanosoma brucei parasites. The VSG-exclusion-1 (VEX1) protein binds both telomeric VSG-associated chromatin and VEX2, an ortholog of nonsense-mediated-decay helicase, UPF1. VEX1 and VEX2 assemble in an RNA polymerase-I transcription-dependent manner and sustain the active, subtelomeric VSG-associated transcription compartment. VSG transcripts and VSG coats become highly heterogeneous when VEX proteins are depleted. Further, the DNA replication-associated chromatin assembly factor, CAF-1, binds to and specifically maintains VEX1 compartmentalisation following DNA replication. Thus, the VEX-complex controls VSG-exclusion, while CAF-1 sustains VEX-complex inheritance in association with the active-VSG. Notably, the VEX2-orthologue and CAF-1 in mammals are also implicated in exclusion and inheritance functions. In trypanosomes, these factors sustain a highly effective and paradigmatic immune evasion strategy.
Original language | English |
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Article number | 3023 |
Pages (from-to) | 1-14 |
Number of pages | 14 |
Journal | Nature Communications |
Volume | 10 |
DOIs | |
Publication status | Published - 9 Jul 2019 |
Keywords
- African trypanosome
- nucleolus
- silencing
- telomere
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Wellcome Centre for Anti-Infectives Research
Cook, S., De Rycker, M., Fairlamb, A., Ferguson, M., Field, M., Gilbert, I., Gray, D., Horn, D., Pawlowic, M., Read, K., Wyatt, P. & Wyllie, S.
1/04/17 → 31/03/24
Project: Research
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High-Throughput Decoding of Virulence Mechanisms in African Trypanosomes (Senior Investigator Award)
1/09/13 → 29/02/20
Project: Research