Plasmodium falciparum histones Pf H2A.Z, H3 and H3 modifications and their associations with gene expresssion

The malaria parasite Plasmodium falciparum has an unusually euchromatic genome with poorly conserved positioning of nucleosomes in intergenic sequences and poorly understood mechanisms of gene regulation. Variant histones and histone modifications determine nucleosome stability and recruit trans factors but their combinatorial contribution to gene regulation is unclear. Here we analysed three windows, each of six hours duration during the 48 hour intraerythrocytic lifecycle and showed that the histone H3 acetylations H3K18ac and H3K27ac and the variant histone Pf H2A.Z are enriched together at regulatory sites upstream of genes. H3K18ac and H3K27ac together dynamically mark regulatory regions of genes expressed during the asexual life cycle. Their temporal pattern of enrichment indicates that they accumulate during S phase and mitosis and are retained at regulatory sequences until at least G1 phase and after cessation of expression of the cognate genes. In contrast, we show that H3K4me1 is generally absent from intergenic sequences and thus depleted from putative regulatory elements.