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 Laengst, 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, 17 (6). pp. 741-751. ISSN 1931-3128, 1934-6069
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RED-BLOOD-CELL; MUTUALLY EXCLUSIVE EXPRESSION; MALARIA PARASITES; ERYTHROCYTE INVASION; TRANSCRIPTION FACTORS; BET BROMODOMAINS; VIRULENCE GENES; DNA-BINDING; IN-SILICO; P-TEFB; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III > Prof. Dr. Gernot Längst |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Jul 2019 14:21 |
| Last Modified: | 10 Jul 2019 14:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5321 |
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