2023年12月25日 / 最終更新日 : 2023年12月25日 ad_y ニュース

2023年 新着論文 66　細胞情報学分野から論文が発表されました

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

Nat Commun. 2023 Dec 11;14(1):8200. doi: 10.1038/s41467-023-44043-y.

Authors

Joana R C Faria  1   2   3 , Michele Tinti  4 , Catarina A Marques  4   5 , Martin Zoltner  4   6 , Harunori Yoshikawa  7   8 , Mark C Field  4   9 , David Horn  10

Affiliations

  • 1 Wellcome Centre for Anti-Infectives Research, Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK. joana.correiafaria@york.ac.uk.
  • 2 Biology Department, University of York, York, UK. joana.correiafaria@york.ac.uk.
  • 3 York Biomedical Research Institute, University of York, York, UK. joana.correiafaria@york.ac.uk.
  • 4 Wellcome Centre for Anti-Infectives Research, Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
  • 5 Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, UK.
  • 6 Faculty of Science, Charles University in Prague, Biocev, Vestec, Czech Republic.
  • 7 Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, UK.
  • 8 Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
  • 9 Biology Centre, Czech Academy of Sciences, Institute of Parasitology, České Budějovice, Czech Republic.
  • 10 Wellcome Centre for Anti-Infectives Research, Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK. d.horn@dundee.ac.uk.

Free PMC article

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.

Conflict of interest statement

The authors declare no competing interests.

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