These authors contributed equally to this work.
Identification of a cis-acting DNA–protein interaction implicated in singular var gene choice in Plasmodium falciparum
Article first published online: 4 SEP 2012
© 2012 Blackwell Publishing Ltd
Volume 14, Issue 12, pages 1836–1848, December 2012
How to Cite
Brancucci, N. M. B., Witmer, K., Schmid, C. D., Flueck, C. and Voss, T. S. (2012), Identification of a cis-acting DNA–protein interaction implicated in singular var gene choice in Plasmodium falciparum. Cellular Microbiology, 14: 1836–1848. doi: 10.1111/cmi.12004
Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms
- Issue published online: 19 NOV 2012
- Article first published online: 4 SEP 2012
- Accepted manuscript online: 14 AUG 2012 10:23AM EST
- Manuscript Accepted: 8 AUG 2012
- Manuscript Revised: 6 AUG 2012
- Manuscript Received: 27 JUL 2012
- Swiss National Science Foundation. Grant Numbers: PP00A-110835, PP00P3_130203
Plasmodium falciparum is responsible for the most severe form of malaria in humans. Antigenic variation of P. falciparum erythrocyte membrane protein 1 leads to immune evasion and occurs through switches in mutually exclusive var gene transcription. The recent progress in Plasmodium epigenetics notwithstanding, the mechanisms by which singularity of var activation is achieved are unknown. Here, we employed a functional approach to dissect the role of var gene upstream regions in mutually exclusive activation. Besides identifying sequence elements involved in activation and initiation of transcription, we mapped a region downstream of the transcriptional start site that is required to maintain singular var gene choice. Activation of promoters lacking this sequence occurs no longer in competition with endogenous var genes. Within this region we pinpointed a sequence-specific DNA–protein interaction involving a cis-acting sequence motif that is conserved in the majority of var loci. These results suggest an important role for this interaction in mutually exclusive locus recognition. Our findings are furthermore consistent with a novel mechanism for the control of singular gene choice in eukaryotes. In addition to their importance in P. falciparum antigenic variation, our results may also help to explain similar processes in other systems.