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Defining the chromatin-associated protein landscapes on Trypanosoma brucei repetitive elements using synthetic TALE proteins
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Abstract
Kinetoplastids, such as Trypanosoma brucei , are eukaryotes that likely separated from the main lineage at an exceptionally early point in evolution. Consequently, many aspects of kinetoplastid biology differ significantly from other eukaryotic model systems, including yeasts, plants, worms, flies, and mammals. As in many eukaryotes, the T. brucei genome contains repetitive elements at various chromosomal locations, including centromere- and telomere-associated repeats and interspersed retrotransposon elements. T. brucei also contains intermediate-sized and mini-chromosomes that harbour abundant 177 bp repeat arrays and 70 bp repeat elements implicated in Variable Surface Glycoprotein (VSG) gene switching. In many eukaryotes, repetitive elements are assembled in specialised chromatin such as heterochromatin; however, apart from centromere- and telomere-associated repeats, little is known about chromatin-associated proteins that decorate these and other repetitive elements in kinetoplastids. Here, we utilise affinity selection of synthetic TALE DNA binding proteins designed to target specific repeat elements to identify enriched proteins by proteomics. Validating the approach, a telomere repeat binding TelR-TALE identifies many proteins previously implicated in telomere function. Furthermore, the 70R-TALE designed to bind 70 bp repeats indicates that proteins involved in DNA repair are enriched on these elements that reside adjacent to VSG genes. Interestingly, the 177 bp repeat binding 177R-TALE enriches for many kinetochore proteins, suggesting that intermediate-sized and mini-chromosomes assemble kinetochores related in composition to those located on the main megabase chromosomes. This provides a first insight into the chromatin landscape of repetitive regions of the trypanosome genome with relevance for their mechanisms of chromosome integrity, immune evasion, and cell replication.
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Global quantification of mammalian gene expression control
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Roles of transposable elements in the regulation of mammalian transcription
Fueyo, R., Judd, J., Feschotte, C., & Wysocka, J. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00457-y · Cited by 451
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Metadata
- Authors
- Carloni, R., Devlin, T., Tong, P., Spanos, C., Auchynnikava, T., Rappsilber, J., Matthews, K. R., & Allshire, R. C.
- Affiliations
- Wellcome Centre for Cell Biology (GB)
- University of Edinburgh (GB)
- Corresponding author
- Matthews, Keith R
- Allshire, Robin C
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2026-03-10
- Volume
- 14
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC12975129
- OpenAlex
- W7114793982
- Cited by
- 1
- References
- 2
- Citations by year
- 2026: 1
- Type
- posted content
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/M010996/1)
- Medical Research Council (MR/T04702X/1)
- Wellcome (10.35802/221717, 10.35802/200885, 10.35802/224358, 10.35802/108504, 10.35802/203149, 10.35802/226791)
- Topics
- Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- Trypanosoma brucei, repetitive elements, chromatin proteins, minichromosomes, kinetochore proteins, telomeric repeats, heterochromatin, DNA repair, affinity selection, kinetoplastids, chromosome integrity
- MeSH terms
- Chromatin, DNA-Binding Proteins, Repetitive Sequences, Nucleic Acid, Trypanosoma brucei brucei, Protozoan Proteins, Telomere, Proteomics
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