GSE109599
Characterization of the accessible genome in the human malaria parasite Plasmodium falciparum
Background: Human malaria is a major cause of disease and poverty in developing countries being P. falciparum the most deadly of malaria parasites. To successfully develop and adapt within hosts, P. falciparum undergoes drastic switches in chromatin structure and gene expression, but the identity and function of regulatory elements driving these events remain poorly understood. In this work, we performed genome-wide profiling of chromatin accessibility in two culture-adapted subclones and four developmental stages during the intraerythrocytic development by the Assay for Transposase-Accessible Chromatin by sequencing (ATAC-seq). Results: ATAC Tn5 hypersensitivity sites (THSSs) localize preferentially at known Transcriptional Start Sites (TSSs). Chromatin accessibility by ATAC-seq is predictive of active transcription and of the levels of histone marks H3K9ac and H3K4me3 in a quantitative manner. Our assay allows us to characterize novel regulatory regions including TSS and enhancers-like elements. We show that the dynamics in the accessible chromatin profile matches temporal differences in gene expression during development, and that gene activation occurs concomitantly to DNA binding events. Motif analysis of stage-specific ATAC-seq footprints predicts the in vivo binding sites and function of a number of ApiAP2 transcription factors. Finally, the mutually exclusive expression and epigenetic switch of several clonally variant genes associates with a differential enrichment of ATAC-seq signal at their promoters. Conclusion: Overall, this study allows us to characterize at a genome-wide level cis-regulatory regions likely to play an essential function in the developmental transitions and in clonally variant gene expression in P. falciparum. Overall design: Genome-wide profiling of chromatin accessibility (ATAC-seq) in two P. falciparum culture-adapted subclones and four developmental stages during the intraerythrocytic development.