ABSTRACT Antigenic variation as a strategy to evade the host adaptive immune response has evolved in divergent pathogens. Antigenic variation involves restricted, and often mutually

exclusive, expression of dominant antigens and a periodic switch in antigen expression during infection. In eukaryotes, nuclear compartmentalization, including three-dimensional folding of

the genome and physical separation of proteins in compartments or condensates, regulates mutually exclusive gene expression and chromosomal translocations. In this Review, we discuss the

impact of nuclear organization on antigenic variation in the protozoan pathogens _Trypanosoma brucei_ and _Plasmodium falciparum_. In particular, we highlight the relevance of nuclear

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ESB1 REGULATES MONOALLELIC ANTIGEN EXPRESSION IN _TRYPANOSOMA BRUCEI_ Article Open access 25 July 2022 SPATIAL INTEGRATION OF TRANSCRIPTION AND SPLICING IN A DEDICATED COMPARTMENT SUSTAINS

MONOGENIC ANTIGEN EXPRESSION IN AFRICAN TRYPANOSOMES Article 11 January 2021 GENOMIC DETERMINANTS OF ANTIGEN EXPRESSION HIERARCHY IN AFRICAN TRYPANOSOMES Article Open access 12 March 2025

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Google Scholar  Download references ACKNOWLEDGEMENTS We thank all members of the Siegel lab for valuable discussion and ScI-llustrations Carolin Wedel Grafikdesign for help with the figure

design. A.B.-S. is funded through the CRC 1064 (213249687), an ERC Starting Grant (3D_Tryps 715466), and an ERC Consolidator Grant (SwitchDecoding 101044320) awarded to T.N.S. M.C. is a

Wellcome Investigator (217138/Z/19/Z). Work on this Review has been supported by funds from the University of Cambridge and LMU München strategic partnership scheme. AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * Division of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany Anna Barcons-Simon & T. Nicolai

Siegel * Biomedical Center, Division of Physiological Chemistry, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany Anna Barcons-Simon & T. Nicolai Siegel *

Department of Biochemistry, University of Cambridge, Cambridge, UK Mark Carrington Authors * Anna Barcons-Simon View author publications You can also search for this author inPubMed Google

Scholar * Mark Carrington View author publications You can also search for this author inPubMed Google Scholar * T. Nicolai Siegel View author publications You can also search for this

author inPubMed Google Scholar CONTRIBUTIONS A.B.-S. and T.N.S conceived the main ideas for the Review. A.B.-S. wrote the original draft. A.B.-S., M.C. and T.N.S. reviewed and edited the

paper. T.N.S. prepared the figures. CORRESPONDING AUTHOR Correspondence to T. Nicolai Siegel. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. PEER REVIEW

PEER REVIEW INFORMATION _Nature Microbiology_ thanks Mohamed-Ali Hakimi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. ADDITIONAL INFORMATION

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Barcons-Simon, A., Carrington, M. & Siegel, T.N. Decoding the impact of nuclear organization on antigenic variation in parasites. _Nat Microbiol_ 8, 1408–1418 (2023).

https://doi.org/10.1038/s41564-023-01424-9 Download citation * Received: 22 December 2022 * Accepted: 13 June 2023 * Published: 31 July 2023 * Issue Date: August 2023 * DOI:

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