Monoallelic expression and epigenetic inheritance sustained by a Trypanosoma brucei variant surface glycoprotein exclusion complex

Joana Correia Faria, Lucy Glover, Sebastian Hutchinson, Cordula Boehm, Mark C. Field, David Horn (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)
111 Downloads (Pure)

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 languageEnglish
Article number3023
Pages (from-to)1-14
Number of pages14
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 9 Jul 2019

Keywords

  • African trypanosome
  • nucleolus
  • silencing
  • telomere

Fingerprint Dive into the research topics of 'Monoallelic expression and epigenetic inheritance sustained by a Trypanosoma brucei variant surface glycoprotein exclusion complex'. Together they form a unique fingerprint.

Cite this