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

Journal article

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 Pol I) 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 Pol I 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.

Authors: Berazategui, MA; Goodwin, I; Lansink, LIM; Gull, K; Rudenko, G

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: National Academy of Sciences
• Journal: Proceedings of the National Academy of Sciences
• Volume: 123
• Issue: 6
• Article number: e2531377123
• Publication date: 2026-02-03
• Acceptance date: 2026-01-02
• DOI: 10.1073/pnas.2531377123
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: transcriptional regulation; monoallelic exclusion; expression site body (ESB); trypanosomes; antigenic variation