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Cell Host Microbe. 2018 Apr 11;23(4):557-569.e9. doi: 10.1016/j.chom.2018.03.007.

Chromatin Accessibility-Based Characterization of the Gene Regulatory Network Underlying Plasmodium falciparum Blood-Stage Development.

Author information

1
Radboud University, Faculty of Science, Department of Molecular Biology, Nijmegen, 6525 GA, the Netherlands.
2
School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
3
Radboud University, Faculty of Science, Department of Molecular Developmental Biology, Nijmegen, 6525 GA, the Netherlands.
4
Radboud University, Faculty of Science, Department of Molecular Biology, Nijmegen, 6525 GA, the Netherlands. Electronic address: r.bartfai@science.ru.nl.

Abstract

Underlying 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.

KEYWORDS:

ATAC-seq; Plasmodium falciparum; RNA-seq; chromatin; malaria; regulatory sequences; transcription factor

PMID:
29649445
PMCID:
PMC5899830
DOI:
10.1016/j.chom.2018.03.007
[Indexed for MEDLINE]
Free PMC Article

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