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A factor integrating transcription and repression of surface antigen genes in African trypanosomes
File(s)
Author(s)
Berazategui, MA
Goodwin, I
Lansink, LIM
Gull, K
Rudenko, G
Type
Journal Article
Abstract
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.
Date Issued
2026-02-10
Date Acceptance
2026-01-02
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2026, 123 (6)
URI
URL
DOI
ISSN
0027-8424
Publisher
National Academy of Sciences
Start Page
e2531377123
Journal / Book Title
Proceedings of the National Academy of Sciences of the United States of America
Volume
123
Issue
6
Copyright Statement
© 2026 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
License URL
Identifier
https://doi.org/10.1073/pnas.2531377123
Publication Status
Published
Article Number
e2531377123
Date Publish Online
2026-02-03