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

Faria, J. R.C., Tinti, M., Marques, C. A. , Zoltner, M., Yoshikawa, H., Field, M. C. and Horn, D. (2023) An allele-selective inter-chromosomal protein bridge supports monogenic antigen expression in the African trypanosome. Nature Communications, 14, 8200. (doi: 10.1038/s41467-023-44043-y) (PMID:38081826) (PMCID:PMC10713589)

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. [Abstract copyright: © 2023. The Author(s).]

• Item Type: Articles
• Additional Information: This work was supported by a Wellcome Investigator Award to DH (217105/Z/19/Z) and a Wellcome Trust/Royal Society Sir Henry Dale Fellowship to JFRC (222573/Z/21/Z). We would like to acknowledge the Dundee Imaging Facility, which is supported by a ‘Wellcome Technology Platform’ award [097945/B/11/Z] and the ‘MRC Next Generation Optical Microscopy’ award [MR/K015869/1]. We would like to thank the Imaging and Cytometry Lab in the Bioscience Technology Facility at the University of York. We would also like to acknowledge the FingerPrints Proteomics Facility at the University of Dundee, which is supported by a ‘Wellcome Trust Technology Platform’ award [097945/B/11/Z].
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: De Almeida Marques, Dr Catarina
• Authors: Faria, J. R.C., Tinti, M., Marques, C. A., Zoltner, M., Yoshikawa, H., Field, M. C., and Horn, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © The Authors 2023
• First Published: First published in Nature Communications 14:8200
• Publisher Policy: Reproduced under a Creative Commons licence