Abstract
SummaryUnderlying the development of malaria parasites within erythrocytes and the resulting pathogenicity is a hardwired program that secures proper timing of gene transcription and production of functionally relevant proteins. How stage-specific gene expression is orchestrated in vivo remains unclear. Here, using the assay for transposase accessible chromatin sequencing (ATAC-seq), we identified ∼4,000 regulatory regions in P. falciparum intraerythrocytic stages. The vast majority of these sites are located within 2 kb upstream of transcribed genes and their chromatin accessibility pattern correlates positively with abundance of the respective mRNA transcript. Importantly, these regions are sufficient to drive stage-specific reporter gene expression and DNA motifs enriched in stage-specific sets of regulatory regions interact with members of the P. falciparum AP2 transcription factor family. Collectively, this study provides initial insights into the in vivo gene regulatory network of P. falciparum intraerythrocytic stages and should serve as a valuable resource for future studies.
Highlights
Malaria, caused by infection with parasites of the Plasmodium genus, remains a major health and economic burden (Murray et al, 2012)
We reasoned that this was likely due to the sequence bias of the enzyme (Goryshin et al, 1998), in combination with the distinctly higher GC content of these sequences as compared to the AT-rich intergenic regions (Gardner et al, 2002). To correct for such biases as well as biases introduced during library preparation and sequencing, we performed the same assay on naked, genomic DNA
We reasoned that selecting reads with a size between 50 and 150 bp could increase the signal-to-noise ratio for the detection of transcription factors (TFs)-binding sites
Summary
Malaria, caused by infection with parasites of the Plasmodium genus, remains a major health and economic burden (Murray et al, 2012). The approximately 48 hr intraerythrocytic development of P. falciparum is responsible for most disease symptoms. It involves the invasion, remodeling, consumption, and rupture of human red blood cells while the parasite replicates by schizogony, giving rise to 16–32 new parasites (Cowman et al., 2016). Underlying this development and the pathogenicity of the parasite is a gene expression program that secures proper timing of gene transcription and production of functionally relevant proteins. Despite being a fundamental eukaryotic process and a potential target of drug-based intervention, our understanding of gene expression regulation in Plasmodium is still in its infancy (Painter et al, 2011)
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