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

Joana R. C. Faria (), Michele Tinti, Catarina A. Marques, Martin Zoltner, Harunori Yoshikawa, Mark C. Field and David Horn ()
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Joana R. C. Faria: University of Dundee
Michele Tinti: University of Dundee
Catarina A. Marques: University of Dundee
Martin Zoltner: University of Dundee
Harunori Yoshikawa: University of Dundee
Mark C. Field: University of Dundee
David Horn: University of Dundee

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-44043-y

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