5′ sequence- and chromatin modification-dependent gene expression in Plasmodium falciparum erythrocytic stage

Abstract

Plasmodium falciparum, the human malaria parasite, is evolutionarily distant from other eukaryotes. Genome-wide analyses of transcription-associated proteins have revealed a relative paucity of putative regulatory transcription factors and an abundance of putative chromatin remodeling machinery, suggesting that this parasite has a transcription regulatory system that is distinct from those of other eukaryotes. Here, we have analyzed transcriptional regulation of the peroxiredoxin genes, pf1-cys-prx and pftpx-1, which show different expression patterns in P. falciparum. The reporter assays revealed the presence of putative enhancers in the 5′ regions of these genes. Although pf1-cys-prx shows trophozoite/schizont stage-specific transcription, a putative cis-acting enhancer sequence in pf1-cys-prx was constitutively active when inserted into the 5′ region of pftpx-1. Electrophoretic mobility shift and DNase I footprinting assays showed that this enhancer region is the target of trophozoite/schizont stage-specific DNA binding proteins. In addition, chromatin immunoprecipitation assays showed that the increased levels of histone acetylation in the 5′ region of pf1-cys-prx and pftpx-1 correlate with the transcriptional activity of these genes. Recruitment of PfGCN5 histone acetyltransferase to the pf1-cys-prx enhancer in trophozoite/schizont stage was observed. These results suggest that P. falciparum possesses a sophisticated system of transcriptional regulation during intraerythrocytic stages that is managed by coordinated interactions of unique cis-elements and trans-acting factors and chromatin modifications.