Identification of a cis-acting DNA-protein interaction implicated in singular var gene choice in Plasmodium falciparum

Brancucci, N. M. and Witmer, K. and Schmid, C. D. and Flueck, C. and Voss, Till S.. (2012) Identification of a cis-acting DNA-protein interaction implicated in singular var gene choice in Plasmodium falciparum. Cellular microbiology, Vol. 14, H. 12. pp. 1836-1848.

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Official URL: http://edoc.unibas.ch/dok/A6094217

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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
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Malaria Gene Regulation (Voss)
UniBasel Contributors:Voss, Till S and Fl├╝ck, Christian and Witmer, Kathrin and Schmid, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Nov 2018 13:29
Deposited On:16 Aug 2013 07:29

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