A factor integrating transcription and repression of surface antigen genes in African trypanosomes

• 成果类型: Article
• 署名作者: Berazategui, Maria Agustina; Goodwin, Ione; Lansink, Lianne I. M.; Gull, Keith; Rudenko, Gloria; Sunter, Jack D.; Faria, Joana R. C.; Wheeler, Richard J.; Tiengwe, Calvin
• 署名单位: Imperial College London; University of York - UK; University of Oxford; Oxford Brookes University; University of Edinburgh
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2531377123
• 发表日期: 2026-02-10
• 页码: E2531377123
• 关键词: antigenic variation; monoallelic exclusion; expression site body (ESB); transcriptional regulation; trypanosomes; EXPRESSION SITE; GLYCOPROTEIN GENES; rnai

摘要

Antigenic variation in Trypanosoma brucei (T. brucei) requires monoallelic expression of one variant surface glycoprotein (VSG) from one of the subtelomeric bloodstream form (BSF) expression sites (BESs). This transcription is unusually mediated by RNA polymerase I (RNA PolI) and occurs in a specialized nuclear body, the expression site body (ESB). While factors promoting active BES transcription and silencing inactive BESs are known, how these opposing activities are integrated remains unknown. Here, we identify ESBX (Tb927.3.1660) as a BSF-specific ESB protein necessary for this coordination. We show that ESBX RNAi knockdown prevents RNA PolI localizing to the ESB and reduces active BES transcription, while also derepressing inactive BESs with low processivity transcription. Conversely, ESBX overexpression weakly activates inactive BESs in a distinct manner from ESBX knockdown, leading to processive transcription, without disrupting the active BES or forming supernumerary ESBs. ESBX knockdown causes a similar transcriptomic defect to ESB1 and VEX2 knockdown combined, establishing ESBX as a key factor linking transcriptional activation of the active BES with inactive BES silencing through the VSG exclusion (VEX) phenomenon. This allows us to suggest models for understanding the establishment and maintenance of monoallelic expression critical for parasite immune evasion.