Plasmodium falciparum: Preinitiation complex occupancy of active and inactive promoters during erythrocytic stage

Abstract

Over 80% of Plasmodium falciparum genes are developmentally regulated during the parasite’s life cycle with most genes expressed in a “just in time” fashion. However, the molecular mechanisms of gene regulation are still poorly understood. Analysis of P. falciparum genome shows that the parasite appears to encode relatively few transcription factors homologous to those in other eukaryotes. We used Chromatin immunoprecipitation (ChIP) to study interaction of PfTBP and PfTFIIE with stage specific Plasmodium promoters. Our results indicate that PfTBP and PfTFIIE are bound to their cognate sequence in active and inactive erythrocytic-expressed promoters. In addition, TF occupancy appears to extend beyond the promoter regions, since PfTBP interaction with the coding and 3’ end regions was also detected. No PfTBP or PfTFIIE interaction was detected on csp and pfs25 genes which are not active during the erythrocytic asexual stage. Furthermore, PfTBP and PfTFIIE binding did not appear to correlate with histone 3 and/or 4 acetylation, suggesting that histone acetylation may not be a prerequisite for PfTBP or PfTFIIE promoter interaction. Based on our observations we concluded that the PfTBP/PfTFIIE-containing preinitiation complex (PIC) would be preassembled on promoters of all erythrocytic-expressed genes in a fashion independent of histone acetylation, providing support for the “poised” model. Contrary to the classical model of eukaryotic gene regulation, PIC interaction with Plasmodium promoters occurred independent of transcriptional activity and to the notion that chromatin acetylation leads to PIC assembly.