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.

变异的表面糖蛋白 (VSG) 包裹着布氏锥虫的血流寄生虫和单等位基因 VSG 表达支持致病性所必需的抗原变异。数千个 VSG 基因中的一个由 RNA 聚合酶 I 在称为表达位点体 (ESB) 的单一核结构中转录，但如何实现单等位 VSG 转录仍不清楚。使用 153 种蛋白质的定位筛选，我们发现了一种 ESB 特异性蛋白 1 (ESB1)，它仅定位于 ESB，并且仅在表达 VSG 的生命周期阶段中表达。ESB1 与活性 VSG 启动子附近的 DNA 结合，是 VSG 表达所必需的，过表达会激活非活性 VSG 启动子。从机制上讲，ESB1 是招募 ESB 组件子集（包括 RNA 聚合酶 I）所必需的，这表明 ESB 具有单独组装的子域。