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An allele-selective inter-chromosomal protein bridge supports monogenic antigen expression in the African trypanosome

Author

Listed:
  • Joana R. C. Faria

    (University of Dundee
    University of York
    University of York)

  • Michele Tinti

    (University of Dundee)

  • Catarina A. Marques

    (University of Dundee
    University of Glasgow)

  • Martin Zoltner

    (University of Dundee
    Charles University in Prague, Biocev)

  • Harunori Yoshikawa

    (University of Dundee
    Tokushima University)

  • Mark C. Field

    (University of Dundee
    Institute of Parasitology)

  • David Horn

    (University of Dundee)

Abstract

UPF1-like helicases play roles in telomeric heterochromatin formation and X-chromosome inactivation, and also in monogenic variant surface glycoprotein (VSG) expression via VSG exclusion-factor-2 (VEX2), a UPF1-related protein in the African trypanosome. We show that VEX2 associates with chromatin specifically at the single active VSG expression site on chromosome 6, forming an allele-selective connection, via VEX1, to the trans-splicing locus on chromosome 9, physically bridging two chromosomes and the VSG transcription and splicing compartments. We further show that the VEX-complex is multimeric and self-regulates turnover to tightly control its abundance. Using single cell transcriptomics following VEX2-depletion, we observed simultaneous derepression of many other telomeric VSGs and multi-allelic VSG expression in individual cells. Thus, an allele-selective, inter-chromosomal, and self-limiting VEX1-2 bridge supports monogenic VSG expression and multi-allelic VSG exclusion.

Suggested Citation

  • Joana R. C. Faria & Michele Tinti & Catarina A. Marques & Martin Zoltner & Harunori Yoshikawa & Mark C. Field & David Horn, 2023. "An allele-selective inter-chromosomal protein bridge supports monogenic antigen expression in the African trypanosome," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44043-y
    DOI: 10.1038/s41467-023-44043-y
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    References listed on IDEAS

    as
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