IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-44043-y.html
   My bibliography  Save this article

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

Author

Listed:
  • Joana R. C. Faria

    (University of Dundee
    University of York
    University of York)

  • Michele Tinti

    (University of Dundee)

  • Catarina A. Marques

    (University of Dundee
    University of Glasgow)

  • Martin Zoltner

    (University of Dundee
    Charles University in Prague, Biocev)

  • Harunori Yoshikawa

    (University of Dundee
    Tokushima University)

  • Mark C. Field

    (University of Dundee
    Institute of Parasitology)

  • David Horn

    (University of Dundee)

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.

Suggested Citation

  • Joana R. C. Faria & Michele Tinti & Catarina A. Marques & Martin Zoltner & Harunori Yoshikawa & Mark C. Field & David Horn, 2023. "An allele-selective inter-chromosomal protein bridge supports monogenic antigen expression in the African trypanosome," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44043-y
    DOI: 10.1038/s41467-023-44043-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44043-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44043-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Emma M. Briggs & Federico Rojas & Richard McCulloch & Keith R. Matthews & Thomas D. Otto, 2021. "Single-cell transcriptomic analysis of bloodstream Trypanosoma brucei reconstructs cell cycle progression and developmental quorum sensing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Kevin Monahan & Adan Horta & Stavros Lomvardas, 2019. "LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice," Nature, Nature, vol. 565(7740), pages 448-453, January.
    3. Miguel Navarro & Keith Gull, 2001. "A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei," Nature, Nature, vol. 414(6865), pages 759-763, December.
    4. Amit Kumar Gaurav & Marjia Afrin & Xian Yang & Arpita Saha & S. K. Abdus Sayeed & Xuehua Pan & Zeyang Ji & Kam-Bo Wong & Mingjie Zhang & Yanxiang Zhao & Bibo Li, 2023. "The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. James Budzak & Robert Jones & Christian Tschudi & Nikolay G. Kolev & Gloria Rudenko, 2022. "An assembly of nuclear bodies associates with the active VSG expression site in African trypanosomes," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    6. Joana Faria & Lucy Glover & Sebastian Hutchinson & Cordula Boehm & Mark C. Field & David Horn, 2019. "Monoallelic expression and epigenetic inheritance sustained by a Trypanosoma brucei variant surface glycoprotein exclusion complex," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Changxu Fan & Xiaoyun Xing & Samuel J. H. Murphy & Jennifer Poursine-Laurent & Heather Schmidt & Bijal A. Parikh & Jeesang Yoon & Mayank N. K. Choudhary & Naresha Saligrama & Sytse J. Piersma & Wayne , 2024. "Cis-regulatory evolution of the recently expanded Ly49 gene family," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Sandhya Chandrasekaran & Sergio Espeso-Gil & Yong-Hwee Eddie Loh & Behnam Javidfar & Bibi Kassim & Yueyan Zhu & Yuan Zhang & Yuhao Dong & Lucy K. Bicks & Haixin Li & Prashanth Rajarajan & Cyril J. Pet, 2021. "Neuron-specific chromosomal megadomain organization is adaptive to recent retrotransposon expansions," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. James Budzak & Robert Jones & Christian Tschudi & Nikolay G. Kolev & Gloria Rudenko, 2022. "An assembly of nuclear bodies associates with the active VSG expression site in African trypanosomes," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Juan F. Quintana & Praveena Chandrasegaran & Matthew C. Sinton & Emma M. Briggs & Thomas D. Otto & Rhiannon Heslop & Calum Bentley-Abbot & Colin Loney & Luis de Lecea & Neil A. Mabbott & Annette MacLe, 2022. "Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    5. Mabel Deladem Tettey & Federico Rojas & Keith R. Matthews, 2022. "Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Hien Thi Thu Pham & Stefan Magez & Boyoon Choi & Bolortsetseg Baatar & Joohee Jung & Magdalena Radwanska, 2023. "Neutrophil metalloproteinase driven spleen damage hampers infection control of trypanosomiasis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. François Serra & Andrea Nieto-Aliseda & Lucía Fanlo-Escudero & Llorenç Rovirosa & Mónica Cabrera-Pasadas & Aleksey Lazarenkov & Blanca Urmeneta & Alvaro Alcalde-Merino & Emanuele M. Nola & Andrei L. O, 2024. "p53 rapidly restructures 3D chromatin organization to trigger a transcriptional response," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    8. Anna Trenaman & Michele Tinti & Richard J. Wall & David Horn, 2024. "Post-transcriptional reprogramming by thousands of mRNA untranslated regions in trypanosomes," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    9. Ziad Ibrahim & Tao Wang & Olivier Destaing & Nicola Salvi & Naghmeh Hoghoughi & Clovis Chabert & Alexandra Rusu & Jinjun Gao & Leonardo Feletto & Nicolas Reynoird & Thomas Schalch & Yingming Zhao & Ma, 2022. "Structural insights into p300 regulation and acetylation-dependent genome organisation," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    10. Nimrod Rappoport & Elad Chomsky & Takashi Nagano & Charlie Seibert & Yaniv Lubling & Yael Baran & Aviezer Lifshitz & Wing Leung & Zohar Mukamel & Ron Shamir & Peter Fraser & Amos Tanay, 2023. "Single cell Hi-C identifies plastic chromosome conformations underlying the gastrulation enhancer landscape," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Mathieu Cayla & Christos Spanos & Kirsty McWilliam & Eliza Waskett & Juri Rappsilber & Keith R. Matthews, 2024. "Differentiation granules, a dynamic regulator of T. brucei development," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44043-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.