Epigenetic Regulation and Chromatin Remodeling in Malaria Parasites

Abstract

Plasmodium falciparum, the human malaria parasite, infects two hosts and various cell types, inducing distinct morphological and physiological changes in the parasite in response to different environmental conditions. These variations required the parasite to adapt and develop elaborate molecular mechanisms to ensure its spread and transmission. Recent findings have significantly improved our understanding of the regulation of gene expression in P. falciparum. Here, we provide an up-to-date overview of technologies used to highlight the transcriptomic adjustments occurring in the parasite throughout its life cycle. We also emphasize the complementary and complex epigenetic mechanisms regulating gene expression in malaria parasites. This review concludes with an outlook on the chromatin architecture, the remodeling systems, and how this 3D genome organization is critical in various biological processes.

Keywords: Plasmodium; chromatin architecture; epigenetics; lncRNA; long noncoding RNA; single cell.

Figure 1

Model of single-cell transcriptomes across the Plasmodium life cycle. Cells are colored according to their distinct stage of development. Master ApiAP2 transcription factors are in bold font along with stage-specific or characteristic markers expressed at the particular stages. The model is based on the single-cell atlas of P. berghei parasites (55). Abbreviation: ApiAP2, apicomplexan Apetala2.

Figure 2

Epigenetic mechanisms in Plasmodium. RNA-sequencing platforms (red) contribute to the identification of distinct transcriptomic signatures across the different life stages of Plasmodium. These gene expression patterns define cell function(s) and are under control of master ApiAP2 transcription factors. Nucleosome occupancy and histone modifications (blue) are major factors regulating chromatin condensation. Other epigenetic mechanisms include lncRNAs and DNA methylation patterns (orange). Finally, the overall chromatin landscape is well organized, forming a repressive cluster including telomeres and var genes positioned at opposing poles of centromeres within the nucleus (green). Abbreviations: ApiAP2, apicomplexan Apetala2; lncRNA, long noncoding RNA; RNAP, RNA polymerase; scRNA-seq, single-cell RNA sequencing; HP1, heterochromatin protein 1.

Figure 3

Hi-C data and 3D modeling of the Plasmodium falciparum genome. The chromatin conformation of the parasite genome is captured by Hi-C. Analysis of Hi-C data allows the generation of chromosomal contact maps depicting inter- and intrachromosomal interactions. This technique also enables reliable computer modeling of genome 3D structure. Interchromosomal interactions (left) between telomeres (green) and centromeres (blue) of the parasite genome are highlighted. The intrachromosomal interactions and the 3D model of chromosome 12 have been emphasized (right).