Journal article

A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression

Gabrielle A Josling, Michaela Petter, Sophie C Oehring, Archna P Gupta, Olivier Dietz, Danny W Wilson, Thomas Schubert, Gernot Laengst, Paul R Gilson, Brendan S Crabb, Suzette Moes, Paul Jenoe, Shu Wei Lim, Graham V Brown, Zbynek Bozdech, Till S Voss, Michael F Duffy

CELL HOST & MICROBE | CELL PRESS | Published : 2015

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 invasio..

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Grants

Awarded by ARC


Awarded by Swiss National Science Foundation


Awarded by Novartis Foundation for Medical-Biological Research


Funding Acknowledgements

The authors thank Yen Hoon Luah, Igor Niederwieser and Shamista Selvarajah for technical assistance; Stuart Ralph, Kym Pham, and Mark Bailey for advice; and Christopher Tonkin and Alan Cowman for reagents. This work was supported by ARC grant number DP110100483, the Swiss National Science Foundation (PP00P3_130203), the Novartis Foundation for Medical-Biological Research (08C46), the Emilia-Guggenheim-Schnurr Foundation, OzEMalaR, and the Rudolf Geigy Foundation.