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Stage-specific transcription activator ESB1 regulates monoallelic antigen expression in Trypanosoma brucei
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López-Escobar, Lara, Hänisch, Benjamin, Halliday, Clare, Ishii, Midori, Akiyoshi, Bungo, Dean, Samuel, Sunter, Jack Daniel, Wheeler, Richard John and Gull, Keith (2022) Stage-specific transcription activator ESB1 regulates monoallelic antigen expression in Trypanosoma brucei. Nature Microbiology, 7 (8). pp. 1280-1290. doi:10.1038/s41564-022-01175-z
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Official URL: https://doi.org/10.1038/s41564-022-01175-z
Abstract
Variant surface glycoprotein (VSG) coats bloodstream form Trypanosoma brucei parasites, and monoallelic VSG expression underpins the antigenic variation necessary for pathogenicity. One of thousands of VSG genes is transcribed by RNA polymerase I in a singular nuclear structure called the expression site body (ESB), but how monoallelic VSG transcription is achieved remains unclear. Using a localization screen of 153 proteins we found one, ESB-specific protein 1 (ESB1), that localized only to the ESB and is expressed only in VSG-expressing life cycle stages. ESB1 associates with DNA near the active VSG promoter and is necessary for VSG expression, with overexpression activating inactive VSG promoters. Mechanistically, ESB1 is necessary for recruitment of a subset of ESB components, including RNA polymerase I, revealing that the ESB has separately assembled subdomains. Because many trypanosomatid parasites have divergent ESB1 orthologues yet do not undergo antigenic variation, ESB1 probably represents an important class of transcription regulators.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | Q Science > QH Natural history > QH426 Genetics Q Science > QL Zoology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | |||||||||||||||
| SWORD Depositor: | Library Publications Router | |||||||||||||||
| Library of Congress Subject Headings (LCSH): | Trypanosoma brucei, Gene expression, Antigens -- Genetic aspects, Genetic transcription | |||||||||||||||
| Journal or Publication Title: | Nature Microbiology | |||||||||||||||
| Publisher: | Nature Publishing Group UK | |||||||||||||||
| ISSN: | 2058-5276 | |||||||||||||||
| Official Date: | August 2022 | |||||||||||||||
| Dates: |
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| Volume: | 7 | |||||||||||||||
| Number: | 8 | |||||||||||||||
| Page Range: | pp. 1280-1290 | |||||||||||||||
| DOI: | 10.1038/s41564-022-01175-z | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Open Access | |||||||||||||||
| RIOXX Funder/Project Grant: |
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