The SPARC complex defines RNAPII promoters in Trypanosoma brucei

  1. Desislava P Staneva
  2. Stefan Bresson
  3. Tatsiana Auchynnikava
  4. Christos Spanos
  5. Juri Rappsilber
  6. A Arockia Jeyaprakash
  7. David Tollervey
  8. Keith R Matthews  Is a corresponding author
  9. Robin C Allshire  Is a corresponding author
  1. University of Edinburgh, United Kingdom
  2. The Francis Crick Institute, United Kingdom
  3. Technische Universität, Germany

Abstract

Kinetoplastids are a highly divergent lineage of eukaryotes with unusual mechanisms for regulating gene expression. We previously surveyed 65 putative chromatin factors in the kinetoplastid Trypanosoma brucei. Our analyses revealed that the predicted histone methyltransferase SET27 and the Chromodomain protein CRD1 are tightly concentrated at RNAPII transcription start regions (TSRs). Here we report that SET27 and CRD1, together with four previously uncharacterized constituents, form the SET27 promoter-associated regulatory complex (SPARC), which is specifically enriched at TSRs. SET27 loss leads to aberrant RNAPII recruitment to promoter sites, accumulation of polyadenylated transcripts upstream of normal transcription start sites, and conversion of some normally unidirectional promoters to bidirectional promoters. Transcriptome analysis in the absence of SET27 revealed upregulated mRNA expression in the vicinity of SPARC peaks within the main body of chromosomes in addition to derepression of genes encoding variant surface glycoproteins (VSGs) located in subtelomeric regions. These analyses uncover a novel chromatin-associated complex required to establish accurate promoter position and directionality.

Data availability

The sequencing data generated in this study can be accessed on the NCBI Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/) with accession number GSE208037.The proteomics data generated in this study can be accessed on the Proteomics Identification Database (PRIDE; https://www.ebi.ac.uk/pride/) with accession number PXD036454.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Desislava P Staneva

    Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Stefan Bresson

    Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Tatsiana Auchynnikava

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Christos Spanos

    Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4376-8242
  5. Juri Rappsilber

    Institute of Biotechnology, Technische Universität, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. A Arockia Jeyaprakash

    Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. David Tollervey

    Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2894-2772
  8. Keith R Matthews

    Institute for Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    keith.matthews@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0309-9184
  9. Robin C Allshire

    Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    robin.allshire@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8005-3625

Funding

Medical Research Council (MR/T04702X/1)

  • Desislava P Staneva
  • Keith R Matthews
  • Robin C Allshire

Wellcome Trust (22171)

  • Keith R Matthews

Wellcome Trust (200885)

  • Desislava P Staneva
  • Tatsiana Auchynnikava
  • Robin C Allshire

Wellcome Trust (224358)

  • Desislava P Staneva
  • Tatsiana Auchynnikava
  • Robin C Allshire

Wellcome Trust (222516)

  • Stefan Bresson
  • David Tollervey

Wellcome Trust (202811)

  • A Arockia Jeyaprakash

Wellcome Trust (108504)

  • Juri Rappsilber

Wellcome Trust (203149)

  • Christos Spanos

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jessica K Tyler, Weill Cornell Medicine, United States

Version history

  1. Preprint posted: July 15, 2022 (view preprint)
  2. Received: September 1, 2022
  3. Accepted: September 27, 2022
  4. Accepted Manuscript published: September 28, 2022 (version 1)
  5. Version of Record published: October 14, 2022 (version 2)

Copyright

© 2022, Staneva et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Desislava P Staneva
  2. Stefan Bresson
  3. Tatsiana Auchynnikava
  4. Christos Spanos
  5. Juri Rappsilber
  6. A Arockia Jeyaprakash
  7. David Tollervey
  8. Keith R Matthews
  9. Robin C Allshire
(2022)
The SPARC complex defines RNAPII promoters in Trypanosoma brucei
eLife 11:e83135.
https://doi.org/10.7554/eLife.83135

Share this article

https://doi.org/10.7554/eLife.83135

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