title: 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.
authors.affiliation: Research Institute, International Medical Center of Japan, Tokyo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Komaki-Yasuda
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Okuwaki
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kano
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nagata
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kawazu
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D004912:Erythrocytes / Q000469:parasitology*; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D002843:Chromatin; D004268:DNA-Binding Proteins; D015800:Protozoan Proteins; D054464:Peroxiredoxins; D051548:Histone Acetyltransferases