Abstract:
Gene expression in Plasmodia integrates post-transcriptional regulation with epigenetic marking of
active genomic regions through histone post-translational modifications (PTMs). To generate insights
into the importance of histone PTMs to the entire asexual and sexual developmental cycles of the
parasite, we used complementary and comparative quantitative chromatin proteomics to identify
and functionally characterise histone PTMs in 8 distinct life cycle stages of P. falciparum parasites.
~500 individual histone PTMs were identified of which 106 could be stringently validated. 46 individual
histone PTMs and 30 co-existing PTMs were fully quantified with high confidence. Importantly, 15 of
these histone PTMs are novel for Plasmodia (e.g. H3K122ac, H3K27me3, H3K56me3). The comparative
nature of the data revealed a highly dynamic histone PTM landscape during life cycle development,
with a set of histone PTMs (H3K4ac, H3K9me1 and H3K36me2) displaying a unique and conserved
abundance profile exclusively during gametocytogenesis (P < 0.001). Euchromatic histone PTMs are abundant during schizogony and late gametocytes; heterochromatic PTMs mark early gametocytes.
Collectively, this data provides the most accurate, complete and comparative chromatin proteomic
analyses of the entire life cycle development of malaria parasites. A substantial association between
histone PTMs and stage-specific transition provides insights into the intricacies characterising
Plasmodial developmental biology.
