PreprintCited by 13Genomics and Chromatin DynamicsTrypanosoma species research and implicationsNuclear Structure and Function

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The SPARC complex defines RNAPII promoters in Trypanosoma brucei

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Preprint — published as 10.7554/elife.83135 · Paper page

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.

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Metadata

Authors
Staneva, D. P., Bresson, S., Auchynnikava, T., Spanos, C., Rappsilber, J., Jeyaprakash, A. A., Tollervey, D., Matthews, K. R., & Allshire, R. C.
Affiliations
  • Wellcome Centre for Cell Biology (GB)
  • The Francis Crick Institute (GB)
  • University of Edinburgh (GB)
Corresponding author
  • Matthews, Keith R.
  • Allshire, Robin C.
Venue
eLife
Publisher
openRxiv
Published
2022-07-15
Volume
11
ISSN
2050-084X (ISSN-L)
OpenAlex
W4297458009
Cited by
13
References
1
Citations by year
2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 1
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Wellcome Trust (222516, 224358, 222516/Z/21/Z, 200885, 221717, 202811/Z/16/Z, 202811, 22171, 108504, 200885/Z/16/Z, 224358/Z/21/Z, 203149, 221717/Z/20/Z)
  • Medical Research Council Canada (MR/T04702X/1)
  • Medical Research Council (MR/T04702X/1, 203149)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
bidirectional promoter, histone methyltransferase, Trypanosoma brucei, variant surface glycoprotein, subtelomeric regions, polyadenylated transcripts, transcriptional derepression
MeSH terms
Histone Methyltransferases, Chromatin, Heterochromatin, RNA Polymerase II, RNA, Messenger, Transcription, Genetic, Trypanosoma brucei brucei, Variant Surface Glycoproteins, Trypanosoma

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