Chromatin-mediated epigenetic regulation in the malaria parasite Plasmodium falciparum

Abstract

Malaria is a major public health problem in many developing countries, with the malignant tertian parasite Plasmodium falciparum causing the most malaria-associated mortality. Extensive research, especially with the advancement of genomics and transfection tools, has highlighted the fundamental importance of chromatin-mediated gene regulation in the developmental program of this early-branching eukaryote. The Plasmodium parasite genomes reveal the existence of both canonical and variant histones that make up the nucleosomes, as well as a full collection of conserved enzymes for chromatin remodeling and histone posttranslational modifications (PTMs). Recent studies have identified a wide array of both conserved and novel histone PTMs in P. falciparum, indicating the presence of a complex and divergent "histone code." Genome-wide analysis has begun to decipher the nucleosome landscape and histone modifications associated with the dynamic organization of chromatin structures during the parasite's life cycle. Focused studies on malaria-specific phenomena such as antigenic variation and red cell invasion pathways shed further light on the involvement of epigenetic mechanisms in these processes. Here we review our current understanding of chromatin-mediated gene regulation in malaria parasites, with specific reference to exemplar studies on antigenic variation and host cell invasion.

Fig. 1.

Schematic drawing of a nucleosome with the four canonical histones (H3, H4, H2A, and H2B) in P. falciparum. The covalent PTMs of the histone tails (methylation [Me], acetylation [Ac], and ubiquitination [Ub]) and enzymes catalyzing the addition of the PTMs (PfGCN5, PfSET1, PfSET2, PfCARM1, PfPRMT1, PfMYST, and PfSET8) are highlighted. PTMs on the tails of variant histones are listed in Table 1.