Stage-specific transcription activator ESB1 regulates monoallelic antigen expression in Trypanosoma brucei

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. The Trypanosoma brucei protein ESB1 is specific to the expression site body, where it activates pathogen monoallelic antigen transcription.

• Publication year

  2022

• Venue

  Nature Microbiology

• Publication date

  2022-07-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/s41564-022-01175-zPMID 35879525PMCID 9352583
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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