University of Cambridge > > Parasitology Seminars > From tagging to transcription activation in trypanosomes

From tagging to transcription activation in trypanosomes

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If you have a question about this talk, please contact Anna Protasio.

This is a hybrid talk. You can attend in person or via zoom. See abstract for details

Monoallelic expression of a single gene family member underpins a molecular “arms race” between many pathogens and their host, through host monoallelic immunoglobulin and pathogen monoallelic antigen expression. In Trypanosoma brucei, a single, abundant, variant surface glycoprotein (VSG) covers the entire surface of the bloodstream parasite and monoallelic VSG transcription underpins their archetypal example of antigenic variation. It is vital for pathogenicity, only occurring in mammalian infectious forms. Transcription of one VSG gene is achieved by RNA polymerase I (Pol I) in a singular nuclear structure: the expression site body (ESB). How monoallelic expression of the single VSG is achieved is incompletely understood and no specific ESB components are known. Here, using a protein localisation screen in bloodstream parasites, we discovered the first ESB -specific protein: ESB1 . It is specific to VSG -expressing life cycle stages where it associates with DNA near the 12 active promoter, is necessary for VSG expression, and its overexpression activates inactive VSG promoters. This showed monoallelic VSG transcription requires a stage-specific transcription activator. Furthermore, ESB1 is necessary for Pol I recruitment to the ESB , while transcript processing and inactive VSG gene exclusion ESB sub-domains do not require ESB1 . This shows that the cellular solution for monoallelic transcription is a complex factory of functionally distinct and separably assembled sub-domains.

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This talk is part of the Parasitology Seminars series.

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