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

Publication date: 11 April 2018
Source:Cell Host & Microbe, Volume 23, Issue 4
Author(s): Christa Geeke Toenhake, Sabine Anne-Kristin Fraschka, Mahalingam Shanmugiah Vijayabaskar, David Robert Westhead, Simon Jan van Heeringen, Richárd Bártfai
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.

Graphical abstract

Teaser

Proliferation of malaria parasites in human erythrocytes requires the expression of functionally related sets of proteins in a "just-in-time" manner. Toenhake et al. map the chromatin structure of blood-stage P. falciparum and use it to dissect the interplay between DNA elements and transcription factors controlling gene expression during intraerythrocytic development.


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