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A comprehensive epigenome map of Plasmodium falciparum reveals unique mechanisms of transcriptional regulation

ABSTRACT: Epigenetic mechanisms have been poorly understood in Plasmodium falciparum, the causative agent of malaria. To elucidate stage specific epigenetic regulations in P. falciparum, we performed genome-wide mapping of various histone modifications, nucleosomes and RNA Polymerase II. Our comprehensive analysis suggest that transcription initiation and elongation are distinct in Plasmodium. In this study, by analyzing histone modifications, nucleosome occupancy and RNA Polymerase II (Pol II) at three different IEC developmental stages of Plasmodium; ring, trophozoite and schizont, we tried to unravel the epigenetic mechanism associated with gene regulation.

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE63369 | GEO | 2015/09/23

SECONDARY ACCESSION(S): PRJNA267591

REPOSITORIES: GEO

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A comprehensive epigenome map of Plasmodium falciparum reveals unique mechanisms of transcriptional regulation

Project description:Epigenetic mechanisms have been poorly understood in Plasmodium falciparum, the causative agent of malaria. To elucidate stage specific epigenetic regulations in P. falciparum, we performed genome-wide mapping of various histone modifications, nucleosomes and RNA Polymerase II. Our comprehensive analysis suggest that transcription initiation and elongation are distinct in Plasmodium. In this study, by analyzing histone modifications, nucleosome occupancy and RNA Polymerase II (Pol II) at three different IEC developmental stages of Plasmodium; ring, trophozoite and schizont, we tried to unravel the epigenetic mechanism associated with gene regulation. Examination of H3K27me3, H3K4me3, H3K9me3, H3K14ac, H3K4me1, H3K79me3, H3K27ac, H3K4me2, H3K9ac, H4ac, RNA Pol II and Histone H3 at three different stages of Plasmodium falciparum

2015-09-23 | E-GEOD-63369 | biostudies-arrayexpress

Dynamics of H3K64 trimethylation on histone core regulates the schizont specific expression of exported proteins in Plasmodium falciparum

Project description:We identified unconventional histone lysine trimethylation mark in the nucleosome core at H3K64 position in human malaria parasite Plasmodium falciparum. Global ChIP analysis was performed using anti-H3K64me3 specific antibody for three major blood stages, i.e. ring, trophozoite and schizont stages to identify the genomic position of the H3K64me3. The sheared chromatin was prepared from highly synchronous P. falciparum culture and subjected for ChIP followed by library preparation from the ChIP DNA and were subjected to sequencing using the HiSeq Illumina platform. H3K64me3 binding sites were determined after sequence alignment and normalization with input sequence. Interestingly, there was a significant reduction in the number of peaks on different chromosomes during multinucleated schizont stage as compared to ring and trophozoite stage. Collectively, this is first study to show that H3K64me3 function as repressor methyl mark during ring and trophozoite stages to regulate the expression of schizont specific export family of proteins in P. falciparum.

2020-07-18 | GSE154651 | GEO

Transcriptional alteration in malaria parasite after disruption of PfPRMT5 [Array]

Project description:Purpose: this study is to analyze the change of overall transctiption after disruption of Protein Arginine Methyltranferase 5 (PRMT5) in Plasmodium falciparum. Methods: In this study, the transcriptomes of a PfPRMT5 gene knockout (KO) parasite line with its wildtype control were analyzed a custom-desinged Agilent microarray.Total RNA were harvested from the asexual parasites at four stages (ring, early trophozoite, late trophozoite, and schizont)(12h, 24h, 36h, and 46h post-invasion) using the Quick-RNA MiniPrep kit (Zymo Research).

2023-06-28 | GSE199419 | GEO

RNA-seq of the malaria parasite Plasmodium falciparum 3D7 during its intraerythrocytic development cycle

Project description:The parasite Plasmodium falciparum is responsible for severe malaria, which is still one of the major causes of death in developing countries. To provide a new RNA-seq reference dataset for its blood-stage transcriptome according to current guidelines and best practices, we performed a time course experiment with three independent biological replicates of synchronized P. falciparum 3D7 cells, that were cultivated at a haematocrit of 5% in human O+ erythrocytes. RNA-seq samples were taken at 8 developmental stages including young ring stage (8 hpi), late ring stage/early trophozoite (16 hpi), mid-age trophozoite (24 hpi), late trophozoite (32 hpi), early schizont (40 hpi), schizont (44 hpi), late schizont (48 hpi) and purified merozoites (0 hpi). Red blood cell pellets were lysed with Trizol and total RNA was purified using column-based purification (PureLink RNA Kit) including DNase treatment on the column and controlling for absence of genomic DNA contamination using qPCR. Whole blood total RNA samples were depleted of human globin mRNA using magnetic bead isolation technology (GLOBINclear kit). After RNA sample quality control and optimized cDNA libraries preparation for AT-biased genomes for Illumina sequencing, RNA-seq was performed at BGI Genomics (Shenzhen, China) on HiSeq 4000 to generate 100 bp paired-end sequencing reads.

2019-07-02 | E-MTAB-7731 | biostudies-arrayexpress

Identification of genome-wide binding sites of Plasmodium falciparum GCN5-acetyltransferase

Project description:Genome-wide ChIP-sequencing analysis of PfGCN5 was carried out in asynchronous stage (trophozoite and schizont stage enriched) parasites using PfGCN5 antibodies. We have observed that PfGCN5 is majorly associated with promoter regions of genes. Moreover, a uniform distribution was found in exons, transcription termination site, and intergenic regions. This study shed some light on PfGCN5 binding sites on Plasmodium falciparum genome.

2020-01-01 | GSE142803 | GEO

Comparative profiling of the heterochromatin landscape in different life cycle stages, strains and species of malaria parasites

Project description:Heterochromatin is a tightly packaged form of DNA that leads to permanent or temporal gene silencing. In P. falciparum heterochromatin is formed after trimethylation of lysine 9 on histone H3 and consequent binding of heterochromatin protein 1 (HP1). Genome-wide profiling studies established that in P. falciparum blood stage schizonts heterochromatin is formed at subtelomeres and some intra-chromosomal islands. Reversible silencing of genes located in these regions has been shown to be key to, among others, antigenic variation, invasion pathway selection or commitment to gametocytogenesis. However, heterochromatic gene silencing has not been investigated in many other Plasmodium species, strains or life cycle stages, yet. Here, we used ChIP-seq to profile HP1 occupancy in asexual parasites of six different species (P. falciparum, P. knowlesi, P. vivax, P. berghei, P. yoelii, and P. chabaudi) and of four different P. falciparum strains (3D7, PF2004, NF54, NF135) as well as two different P. knowlesi clones (A1C1, A1H1). Additionally, we performed HP1 ChIP-seq on three asexual stages (ring, trophozoite and schizont stage) and two sexual stages of P. falciparum parasites. Collectively, the generated HP1 profiles provide a detailed catalog of heterochromatic genes and reveal conserved and specialized features of epigenetic control at different life cycle stages, strains and species across the genus Plasmodium.

2018-01-16 | GSE102695 | GEO

The Plasmodium falciparum Nuclear Protein Phosphatase NIF4 is Required for Efficient Merozoite Invasion and Regulates Artemisinin Sensitivity

Project description:Artemisinin resistance in Plasmodium falciparum, clinically presented as prolonged parasite clearance half-life, has been associated with a mutation in the NLI-interacting factor-like phosphatase PfNIF4, in addition to the mutations in the Kelch13 protein as the major determinant. We found that PfNIF4 predominant expression at the schizont stage and localized in the nuclei of the parasite. To elucidate the functions of PfNIF4 in P. falciparum, we performed PfNIF4 knockdown (KD) using the inducible ribozyme system. PfNIF4 KD attenuated merozoite invasion and affected gametocytogenesis. PfNIF4 KD parasites also showed significantly increased in vitro susceptibility to artemisinins. Transcriptomic analysis revealed that PfNIF4 KD led to significant changes in the expression of approximately 10-25% of parasite genes during the IDC. At the schizont stage, down-regulated genes were significantly enriched in the invasion-related terms, while at the trophozoite and schizont stages, pathways associated with artemisinin resistance (e.g., mitochondrial function, membrane, and Kelch13 interactome) were also down-regulated. Consistent with PfNIF4 being a protein phosphatase, PfNIF4 KD resulted in an overall up-regulation of the phosphoproteome of infected erythrocytes. Specifically, we observed increased phosphorylation of Ser2/5 of the tandem repeats in the Rpb1 C-terminal domain (CTD) of RNA polymerase II (RNAPII) upon PfNIF4 KD. Furthermore, using the TurboID-based proteomic approach, we identified that PfNIF4 interacted with the RNA polymerase II (RNAPII) components, AP2-domain transcription factors, and chromatin-modifiers and binders. These findings suggest that PfNIF4 may act as the RNAPII CTD phosphatase, regulating the expression of general and parasite-specific cellular pathways during the blood-stage development.

2022-07-23 | PXD033957 | Pride

The Plasmodium falciparum Nuclear Protein Phosphatase NIF4 is Required for Efficient Merozoite Invasion and Regulates Artemisinin Sensitivity

2022-07-23 | PXD030249 | Pride

The Plasmodium falciparum Nuclear Protein Phosphatase NIF4 is Required for Efficient Merozoite Invasion and Regulates Artemisinin Sensitivity

2022-07-23 | PXD034167 | Pride

A High Parasite Density Environment Induces Transcriptional Changes and Cell Death in Plasmodium falciparum Blood Stages

Project description:Transient regulation of Plasmodium numbers below the density that induces fever has been observed in chronic malaria infections in humans and this species transcending control cannot be explained by immunity alone. Using an in vitro system we have observed density dependent regulation of malaria parasitemia as a mechanism to possibly explain these in vivo observations. P. falciparum blood stages from a high but not low-density environment exhibited what appeared to be programmed changes during the late trophozoite and schizont stages of the intraerythrocytic cycle.

2017-12-31 | GSE91188 | GEO

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