Abstract:
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Human malaria is a devastating disease and a major cause of poverty in resource-limited countries. To develop and adapt
within hosts Plasmodium falciparum undergoes drastic switches in
gene expression. To identify regulatory regions in the parasite
genome, we performed genome-wide profiling of chromatin
accessibility in two culture-adapted isogenic subclones at four
developmental stages during the intraerythrocytic cycle by using
the Assay for Transposase-Accessible Chromatin by sequencing
(ATAC-seq). Tn5 transposase hypersensitivity sites (THSSs)
localize preferentially at transcriptional start sites (TSSs).
Chromatin accessibility by ATAC-seq is predictive of active
transcription and of the levels of histone marks H3K9ac and
H3K4me3. Our assay allows the identification of novel regulatory
regions including TSS and enhancer-like elements. We show that
the dynamics in the accessible chromatin profile matches
temporal transcription during development. Motif analysis of
stage-specific ATAC-seq sites predicts the in vivo binding sites
and function of multiple ApiAP2 transcription factors. At last,
the alternative expression states of some clonally variant genes
(CVGs), including eba, phist, var and clag genes, associate with
a differential ATAC-seq signal at their promoters. Altogether,
this study identifies genome-wide regulatory regions likely to
play an essential function in the developmental transitions and
in CVG expression in P. falciparum. |