Abstract
Gene expression during the intraerythrocytic development cycle of the human malarial parasite Plasmodium falciparum is subject to tight temporal control, resulting in a cascade of gene expression to meet the physiological demands of growth, replication, and reinvasion. The roles of the different molecular mechanisms that drive this temporal program of gene expression are poorly understood. Here we report the use of the bxb1 integrase system to reconstitute all aspects of the absolute and temporal control of the prototypical housekeeping gene encoding the proliferating cell nuclear antigen (Pfpcna) around an integrated luciferase reporter cassette. A quantitative analysis of the effect of the serial deletion of 5′ and 3′ genetic elements and sublethal doses of histone deacetylase inhibitors demonstrates that while the absolute control of gene expression could be perturbed, no effect on the temporal control of gene expression was observed. These data provide support for a novel model for the temporal control of potentially hundreds of genes during the intraerythrocytic development of this important human pathogen.
Original language | English |
---|---|
Pages (from-to) | 205-221 |
Number of pages | 17 |
Journal | Journal of Molecular Biology |
Volume | 408 |
Issue number | 2 |
DOIs | |
Publication status | Published - 29 Apr 2011 |
Bibliographical note
Funding Information:We would like to thank David Fidock (Columbia University) and Kathy Andrews (Queensland Institute of Medical Research) for their kind gifts of materials for this study, and Karen Russell for her kind reading of this manuscript. This work was supported by a New Investigator Award from the Biotechnology and Biological Sciences Research Council ( BB/H002405/1 ) and a Royal Society Relocation fellowship ( 502014.K515 ) to P.H. E.H.W. was supported by a Graduate Teaching Assistantship provided by Keele University Medical School.
Keywords
- EMSA
- epigenetic
- gene regulation
- malaria
- posttranscriptional
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology