Transcriptional profiling defines histone acetylation as a regulator of gene expression during human-to-mosquito transmission of the malaria parasite Plasmodium falciparum

Transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by the intraerythrocytic gametocytes, which, once taken up during a blood meal, become activated to initiate sexual reproduction. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they are crucial for spreading the tropical disease. During gametocyte maturation, different repertoires of genes are switched on and off in a well-coordinated sequence, pointing to regulatory mechanisms of gene expression. While epigenetic gene control has been studied during erythrocytic schizogony of P. falciparum, little is known about this process during parasite human-to-mosquito transmission of the parasite. To unveil the potential role of histone acetylation during gene expression in gametocytes, we carried out a microarray-based transcriptome analysis on gametocytes treated with the histone deacetylase inhibitor trichostatin A (TSA). Plasmodium falciparum Percoll enriched immature (stages II-IV) gametocytes (imGC), mature (stage V) gametocytes (mGC) and gametocytes at 1 h post-activation with 100 µM Xanthurenic acid at RT (aGC) were obtained. Each enriched gametocyte sample was treated with TSA at IC90 concentrations (0.26 µM) or with 0.5% vol. ethanol (untreated control) for 1 h and 6 h, respectively and total RNA was isolated using the Trizol reagent (Invitrogen) according to the manufacturer’s protocol. The extracted RNA was then processed for microarray analysis.