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A Plasmodium falciparum bromodomain protein regulates invasion gene expression

Josling, Gabrielle A. and Petter, Michaela and Oehring, Sophie C. and Gupta, Archna P. and Dietz, Olivier and Wilson, Danny W. and Schubert, Thomas and Längst, Gernot and Gilson, Paul R. and Crabb, Brendan S. and Moes, Suzette and Jenoe, Paul and Lim, Shu Wei and Brown, Graham V. and Bozdech, Zbynek and Voss, Till S. and Duffy, Michael F.. (2015) A Plasmodium falciparum bromodomain protein regulates invasion gene expression. Cell host & microbe, Vol. 17, H. 6. pp. 741-751.

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Official URL: http://edoc.unibas.ch/dok/A6391028

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Abstract

During red-blood-cell-stage infection of Plasmodium falciparum, the parasite undergoes repeated rounds of replication, egress, and invasion. Erythrocyte invasion involves specific interactions between host cell receptors and parasite ligands and coordinated expression of genes specific to this step of the life cycle. We show that a parasite-specific bromodomain protein, PfBDP1, binds to chromatin at transcriptional start sites of invasion-related genes and directly controls their expression. Conditional PfBDP1 knockdown causes a dramatic defect in parasite invasion and growth and results in transcriptional downregulation of multiple invasion-related genes at a time point critical for invasion. Conversely, PfBDP1 overexpression enhances expression of these same invasion-related genes. PfBDP1 binds to acetylated histone H3 and a second bromodomain protein, PfBDP2, suggesting a potential mechanism for gene recognition and control. Collectively, these findings show that PfBDP1 critically coordinates expression of invasion genes and indicate that targeting PfBDP1 could be an invaluable tool in malaria eradication.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Gene Regulation (Voss)
UniBasel Contributors:Voss, Till S
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:1931-3128
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:03 Jul 2015 08:53
Deposited On:03 Jul 2015 08:53

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