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 (Pol I) in a singular nuclear structure called the expression site body (ESB) but how monoallelic VSG transcription is achieved remains unclear. Using a localisation screen of 153 proteins, we found one, ESB-specific protein 1 (ESB1), which localised 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 Pol I, revealing the ESB has separately assembled sub-domains. As many trypanosomatid parasites have divergent ESB1 orthologs yet do not undergo antigenic variation, ESB1 likely represents an important class of transcription regulators.
López-Escobar, LaraHänisch, BenjaminHalliday, ClareIshii, MidoriAkiyoshi, BungoDean, SamuelSunter, Jack D.
Wheeler, Richard J.Gull, Keith
Department of Biological and Medical Sciences
Year of publication: 2022Date of RADAR deposit: 2022-06-28