Role of H4K8ac in P. falciparum life cycle
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA328387 | ENA |
REPOSITORIES: ENA
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Project description:Erythrocyte invasion is an essential step in the life cycle of the malaria parasite Plasmodium falciparum that involves specific interactions between host cell receptors and parasite ligands. How the parasite regulates the expression of invasion-related genes is to date largely unknown. Here we show that a novel, parasite-specific bromodomain protein (PfBDP1) binds to chromatin at the transcriptional start site 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 down-regulation of multiple invasion-related genes at a time point critical for invasion. This is the first report of a histone binding protein that activates genes in P. falciparum and our data place PfBDP1 in a central position for controlling the coordinated expression of invasion genes. Bromodomains are emerging therapeutic targets and drugs that specifically inhibit PfBDP1 could be an invaluable tool in the effort to eradicate malaria. P. falciparum 3D7 parasites over-expressing PfBDP1-3xHA (3D7/PfBDP1 OE) [PMID: 23181666] were grown in presence of 5μg/ml BSD-S-HCl. The parasite line 3D7/cam [PMID: 22435676.] grown under the same conditions and expressing hDHFR instead of PfBDP1-3xHA from the same promoter was used as control. RNA extracted from these samples at four consecutive time points each was processed for microarray analysis.
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