Chromatin accessibility based characterization of gene regulatory network of P. falciparum blood stage development
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA408158 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6055330_1.fastq.gz | Fastqsanger.gz | |||
| SRR6055330_2.fastq.gz | Fastqsanger.gz | |||
| SRR6055340.fastq.gz | Fastqsanger.gz | |||
| SRR6055331_1.fastq.gz | Fastqsanger.gz | |||
| SRR6055331_2.fastq.gz | Fastqsanger.gz |
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Project description:We present ATAC-seq combined with direction RNA seq data for eight time points across the intraerythorcytic development cycle of Plasmodium falciparum 3D7. ATAC peaks were called by MACS2 using ATAC-seq libraries generated with genomic DNA as a control. The majority of identified ATAC peaks were located in intergenic regions and captured most (95%) of previously identified binding sites of the transcription factor required for the expression of most invasion-related genes PfAP2-I (Santos et al., 2017). The robustness of the ATAC-seq dataset was confirmed with a second biological replicate both in terms of peak location and relative peak accessibility pattern. Peaks were assigned to the closest gene and the majority of peaks showed a clear positive correlation between chromatin accessibility pattern and relative mRNA abundance (Pearson correlation > 0.6). In addition, they were sufficient to drive the stage-specific expression of a reporter gene, demonstrating their functionality. Motif searches restricted to accessible regions showed enrichment of several predicted Plasmodium motifs while also predicting several novel regulatory elements.
2018-04-11 | GSE104075 | GEO
Project description: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.
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Project description:Systems biology approaches that are based on gene expression and bioinformatics analysis have been successful in predicting the functions of many genes in Plasmodium falciparum, a protozoan parasite responsible for most of the deaths due to malaria. However, methods that can provide information about the biological processes that are active in this parasite during complicated malaria conditions have not been employed yet. Here, we report the use of a weighted gene co-expression-based network analysis approach to construct a P. falciparum in vivo systems network. Gene expression profiles of 21 P. falciparum clinical isolates were utilized to construct the same. A total of 20 highly interacting modules were identified post network creation, of which at least 10% members of 12 modules were found to be differentially regulated in complicated isolates compared to uncomplicated isolates. Enrichment analysis identified biological processes like oxidation-reduction, electron transport chain, protein synthesis, ubiquitin-dependent catabolic processes, RNA binding and purine nucleotide metabolic processes to be associated with these modules. Additionally, for each module, highly connected hub genes were identified. Detailed functional analysis of many hub genes with known annotated function underline their importance in parasite development and survival, suggesting that other hub genes with unknown function might be playing crucial roles in parasite biology and are potential candidate for intervention strategies.
2016-01-30 | GSE64931 | GEO
Project description: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.
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