The histone methyltransferase PfSET2 regulates gene expression crucial for gametocyte development

Abstract text

The intracellular and extracellular survival of the malaria parasite Plasmodium falciparum in the human and mosquito hosts is dependent on rapid morphological and physiological changes, which are coordinated by various gene regulation mechanisms. Growing evidence suggests the contribution of epigenetic control mechanisms, in particular histone post-translational modifications, during intraerythrocytic replication and immune evasion of the asexual blood stage parasites. In contrast, the role of histone post-translational modifications during the sexual development of the parasite is not well studied. Previously conducted chemical loss-of-function studies by Ngwa et al. (2019), using the histone methyltransferase inhibitor BIX-01294, reveiled significant changes in the gene expression pattern of gametocytes and an impairment in gametocyte development and gametogenesis. In this study, we aimed to investigate the role of the histone methyltransferase PfSET2, one of ten known SET proteins of P. falciparum, in gene regulation during gametocyte development. We show that PfSET2 is expressed in the asexual and sexual blood stages. PfSET2 gene disruption results in changes in the histone methylation and gene expression patterns of the asexual blood stages and in the abrogation of gametocyte development. Our data point to a pivotal function of PfSET2 in the epigenetic regulation of gene expression crucial for gametocyte vitality.