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, David Horn*

*Corresponding author for this work

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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.

Original languageEnglish
Article number8200
Number of pages18
JournalNature Communications
Issue number1
Publication statusPublished - 11 Dec 2023

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