Yet to SET: Plasmodium falciparum Histone Lysine Methyltransferases

Abstract

Malaria caused by Plasmodium falciparum continues to remain a global health challenge. Its prevention, treatment and elimination efforts are threatened by the inevitable emergence of drug resistance to currently effective treatment regimes. New antimalarials with distinct modes of action and multistage and multispecies activity will be an important addition to the arms race against the malarial parasite. P. falciparum’s epigenome represents a promising target in this battle and offers exciting opportunities for targeted intervention. With an unusually AT-rich genome, a relative paucity of specific transcription factors and limited heterochromatin, epigenetic control has emerged as an important contributor to P. falciparum’s survival and virulence. P. falciparum histones are marked dynamically with a vast array of post translational modifications. These include several well studied and some novel marks. The parasite has an epigenetic signature distinct from its host and shows several parasite-specific adaptations. The regulators of these marks remain understudied, however. While histone acetylation and its regulators have been more extensively studied in the field, research on other epigenetic effectors is also catching up. This review highlights the research efforts aimed at understanding the role of the parasite’s histone lysine methyltransferases in shaping transcriptional regulation and the histone modification landscape.