Faria, Joana R.C. orcid.org/0000-0001-6274-8143, Tinti, Michele, Marques, Catarina A. et al. (4 more authors) (2023) An allele-selective inter-chromosomal protein bridge supports monogenic antigen expression in the African trypanosome. Nature Communications. 8200. ISSN 2041-1723
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2023 |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Centre for Immunology and Infection (CII) (York) |
Depositing User: | Pure (York) |
Date Deposited: | 13 Dec 2023 09:20 |
Last Modified: | 21 Jan 2025 18:11 |
Published Version: | https://doi.org/10.1038/s41467-023-44043-y |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-023-44043-y |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:206582 |
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Filename: s41467-023-44043-y.pdf
Description: An allele-selective inter-chromosomal protein bridge supports monogenic antigen expression in the African trypanosome.
Licence: CC-BY 2.5