Gene transcription across the life cycle of the human malaria parasite Plasmodium falciparum parasite is highly ordered and stage-specific. Histone post-translational modification (PTM) is one of the key gene regulatory mechanisms during the parasite intraerythrocytic developmental cycle. In eukaryotes, PTMs influence gene expression by directly affect chromatin structure or by recruiting regulatory proteins. Histone acetylation is particularly abundant in P. falciparum; it is associated with active gene and is critical for parasite growth. Specific readers, such as bromodomain proteins, are required to read and transduce signal of histone acetylation by interacting with acetylated lysine residues. In P. falciparum, there are eight apicomplexan-specific putative bromodomain proteins. We showed that bromodomain proteins 1 (PfBDP1) is critical for the coordinated regulation of invasion genes and is essential for parasite survival.
Chromatin immunoprecipitation sequencing (ChIP-seq) protocol was successfully optimised to identify PfBDP3 enrichment sites in the P. falciparum genome. During mature schizont stage, PfBDP3 is located upstream of schizont-specific genes as well as near genes which are implicated in sexual commitment or expressed specifically in sexual gametocyte stage. It is also enriched adjacent to genes involved in DNA modulation/repair and lipid biosynthesis. In addition to the ChIP-seq data, we generated an inducible PfBDP3 knockout parasite line to validate its function by determining changes in phenotype as well as differential gene expression (RNA-seq) in the absence of PfBDP3. Overall, these data provide a first insight into the role of PfBDP3 in P. falciparum gene regulation.