Abstract
Over the past decade, we have witnessed significant progresses in understanding gene regulation in Apicomplexa including the human malaria parasite, Plasmodium falciparum. This parasite possesses the ability to convert in multiple stages in various hosts, cell types, and environments. Recent findings indicate that P. falciparum is talented at using efficient and complementary molecular mechanisms to ensure a tight control of gene expression at each stage of its life cycle. Here, we review the current understanding on the contribution of the epigenome, atypical transcription factors, and chromatin organization to regulate stage conversion in P. falciparum. The adjustment of these regulatory mechanisms occurring during the progression of the life cycle will be extensively discussed.
Highlights
Malaria affected 228 million people and 405,000 deaths in 2018 (WHO, 2019) and remains one of the major global health problems
Local modifications play a primordial role with the involvement of nucleosome occupancy, epigenetic modifications, protein modifiers, and long ncRNA (lncRNA) promoting gene activation or silencing
Heterochromatin is enriched in Heterochromatin Protein 1 (HP1), H3K9me3, and H3K36me3 marks while euchromatin exhibits H3K9ac and H3K4me3 marks and a lower nucleosome occupancy facilitating the binding of the general transcriptional machinery in the nucleosome-depleted region (NDR)
Summary
Malaria affected 228 million people and 405,000 deaths in 2018 (WHO, 2019) and remains one of the major global health problems. After a bite by an infected female Anopheles, sporozoites are injected into the human and invade hepatocytes This asymptomatic phase leads to the multiplication of parasites, which are released into the bloodstream and initiate the intraerythrocytic developmental cycle (IDC) inside red blood cells. Advances in single-cell RNA sequencing provided new insights in our understanding of gene expression across different stages and Plasmodium species (Reid et al, 2018; Walzer et al, 2018; Howick et al, 2019; Sà et al, 2020). To ensure this dynamic gene expression, adjustable according to environmental factors and the parasite development, a tight and coordinated regulation is fundamental at each stage. The contribution of epigenetics and chromatin-associated proteins as well as the role of chromatin organization will be detailed, with a particular interest in P. falciparum
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