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Genome-wide localisation of the bromodomain protein PfBDP1 in the malaria parasite P. falciparum

ABSTRACT: During red-blood-cell-stage infection of Plasmodium falciparum, the parasite undergoes repeated rounds of replication, egress, and invasion. Erythrocyte invasion involves specific interactions between host cell receptors and parasite ligands and coordinated expression of genes specific to this step of the life cycle. We show that a parasite-specific bromodomain protein, PfBDP1, binds to chromatin at transcriptional start sites of invasion-related genes and directly controls their expression. Conditional PfBDP1 knockdown causes a dramatic defect in parasite invasion and growth and results in transcriptional downregulation of multiple invasion-related genes at a time point critical for invasion. Conversely, PfBDP1 overexpression enhances expression of these same invasion-related genes. PfBDP1 binds to acetylated histone H3 and a second bromodomain protein, PfBDP2, suggesting a potential mechanism for gene recognition and control. Collectively, these findings show that PfBDP1 critically coordinates expression of invasion genes and indicate that targeting PfBDP1 could be an invaluable tool in malaria eradication.

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE79135 | GEO | 2016/03/22

SECONDARY ACCESSION(S): PRJNA315899

REPOSITORIES: GEO

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Genome-wide localisation of the bromodomain protein PfBDP1 in the malaria parasite P. falciparum

Project description:During red-blood-cell-stage infection of Plasmodium falciparum, the parasite undergoes repeated rounds of replication, egress, and invasion. Erythrocyte invasion involves specific interactions between host cell receptors and parasite ligands and coordinated expression of genes specific to this step of the life cycle. We show that a parasite-specific bromodomain protein, PfBDP1, binds to chromatin at transcriptional start sites of invasion-related genes and directly controls their expression. Conditional PfBDP1 knockdown causes a dramatic defect in parasite invasion and growth and results in transcriptional downregulation of multiple invasion-related genes at a time point critical for invasion. Conversely, PfBDP1 overexpression enhances expression of these same invasion-related genes. PfBDP1 binds to acetylated histone H3 and a second bromodomain protein, PfBDP2, suggesting a potential mechanism for gene recognition and control. Collectively, these findings show that PfBDP1 critically coordinates expression of invasion genes and indicate that targeting PfBDP1 could be an invaluable tool in malaria eradication. ChIPseq mapping of the genome wide enrichment profile of the P. falciparum bromodomain protein PfBDP1 in two parasite stages and correlation with RNAseq expression data

2016-03-22 | E-GEOD-79135 | biostudies-arrayexpress

Whole genome expression profiling across the life cycle of PfBDP1 overexpressing P. falciparum malaria parasites

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ChIPseq of the P. falciparum bromodomain proteins PfBDP7 and PfBDP1 in early and mature schizonts

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Project description:To study the bromodomain protein PfBDP1 in the malaria parasite P. falciparum, a transgenic parasite line was generated (PfBDP1DD) in which PfBDP1 was tagged with a haemagglutinin tag and a ligand regulatable FKBP destabilization domain that allowed conditional knockdown of PfBDP1 by removal of the stabilizing ligand Shld1 from cultures. Shld1 was removed 30 hours post invasion (hpi) and the cells allowed to reinvade fresh red blood cells. The effects of PfBDP1 knockdown on gene expression were assessed by transcriptional profiling on microarrays over 6 consecutive time points (8 hour intervals) in the intraerythrocytic developmental cycle (IDC). Two condition matched time course experiment, PfBDP1DD ON versus OFF Shld1. Transgenic P. falciparum 3D7 parasites (PfBDP1DD) expressing an endogeneous PfBDP1-HA-DD fusion protein were grown in the presence of 2.5 nM WR99210/500 nM Shld1 (PfBDP1DD_ON) or 2.5 nM WR99210 (PfBDP1DD_OFF). After invasion, RNA was extracted at 6 consectutive time points in 8 hour intervals during the IDC, starting at 4 hpi, and was processed for microarray analysis. Three matched biological replicates were performed for both conditions, independently grown and harvested. Each array represents one RNA sample.

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Cell cycle-dependent, intercellular transmission of Toxoplasma gondii is accompanied by marked changes in parasite gene expression.

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Plasmodium falciparum

Project description:Genome-wide localisation of the bromodomain protein PfBDP1 in the malaria parasite P. falciparum

| PRJNA315899 | ENA