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A coordinated regulatory network of ApiAP2 transcription factors involved in heterochromatic gene expression during Plasmodium falciparum blood-stage development [ChIP-Seq]

ABSTRACT: A coordinated regulatory network of ApiAP2 transcription factors involved in heterochromatic gene expression during Plasmodium falciparum blood-stage development [ChIP-Seq]

PROVIDER: PRJNA765872 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16020900_1.fastq.gz	Fastqsanger.gz
	SRR16020900_2.fastq.gz	Fastqsanger.gz
	SRR16021000_1.fastq.gz	Fastqsanger.gz
	SRR16021000_2.fastq.gz	Fastqsanger.gz
	SRR16020901_1.fastq.gz	Fastqsanger.gz

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A coordinated regulatory network of ApiAP2 transcription factors involved in heterochromatic gene expression during Plasmodium falciparum blood-stage development

Project description:A coordinated regulatory network of ApiAP2 transcription factors involved in heterochromatic gene expression during Plasmodium falciparum blood-stage development

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A coordinated regulatory network of ApiAP2 transcription factors involved in heterochromatic gene expression during Plasmodium falciparum blood-stage development [RNA-Seq]

Project description:A coordinated regulatory network of ApiAP2 transcription factors involved in heterochromatic gene expression during Plasmodium falciparum blood-stage development [RNA-Seq]

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A coordinated regulatory network of ApiAP2 transcription factors involved in heterochromatic gene expression during Plasmodium falciparum blood-stage development

Project description:This SuperSeries is composed of the SubSeries listed below.

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A coordinated regulatory network of ApiAP2 transcription factors involved in heterochromatic gene expression during Plasmodium falciparum blood-stage development [ChIP-Seq]

Project description:Genome-wide occupancy of sixteen PfApiAP2 transcription factors and PfHP1 throughout the intraerythrocytic cycle

2022-03-06 | GSE184658 | GEO

A coordinated regulatory network of ApiAP2 transcription factors involved in heterochromatic gene expression during Plasmodium falciparum blood-stage development [RNA-Seq]

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PfAP2-HC, an unusual, heterochromatin-associated ApiAP2 factor of Plasmodium falciparum

Project description:PfAP2-HC, an unusual, heterochromatin-associated ApiAP2 factor of Plasmodium falciparum

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Project description:An ApiAP2 member regulates expression of clonally variant genes of the human malaria parasite Plasmodium falciparum

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Identification of antimalarial compounds that inhibit Apicomplexan AP2 transcription factor proteins in the human malaria parasite Plasmodium falciparum [ChIP-seq]

Project description:Plasmodium parasites are reliant on the Apicomplexan AP2 (ApiAP2) transcription factor family to regulate gene expression programs. AP2 DNA binding domains have no homologs in the human or mosquito host genomes, making them potential antimalarial drug targets. Using an in-silico screen to dock thousands of small molecules into the crystal structure of the AP2-EXP (Pf3D7_1466400) AP2 domain (PDB:3IGM), we identified compounds that interact with this domain. Four compounds were found to compete for DNA binding with AP2-EXP and at least one additional ApiAP2 protein. Our top ApiAP2 competitor compound perturbs the transcriptome of P. falciparum trophozoites and results in a decrease in abundance of log2 fold change > 2 for 50% (46/93) of AP2-EXP target genes. Additionally, two ApiAP2 competitor compounds have multi-stage anti-Plasmodium activity against blood and mosquito stage parasites. In summary, we describe a novel set of antimalarial compounds that are targeted against the ApiAP2 family of proteins. These compounds may be used for future chemical genetic interrogation of ApiAP2 proteins or serve as starting points for a new class of antimalarial therapeutics.

2022-07-15 | GSE208155 | GEO

PfAP2-HC, an unusual, heterochromatin-associated ApiAP2 factor of Plasmodium falciparum

Project description:In this study we have investigated PfAP2-HC (PF3D7_1456000), a protein that was identified by co-immunoprecipitation with PfHP1 coupled with liquid chromatography-tandem mass spectrometry. PfAP2-HC belongs to the ApiAP2 family, the main transcription factor family in Apicomplexan parasites. We have confirmed that AP2-HC colocalises with HP1 with the use of immunofluorescence assays and chromatin immunoprecipitation-sequencing. We show that PfAP2-HC is not required for heterochromatin maintenance and inheritance with the use of PfAP2-HC Kock out and knockdown. We show with transcriptome-wide microarray time course analysis that PfAP2-HC does not act as a transcription factor in blood stage parasites. We demonstrate that the AP2 domain is dispensable for heterochromatin targeting by introducing a premature stop codon before the AP2 domain. We show that PfAP2-HC binding to heterochromatin dependents on PfHP1. and PfAP2-HC is likely not involved in de novo heterochromatin formation

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Project description:The malaria parasite Plasmodium falciparum relies on clonally variant gene expression in order to escape immune recognition and secure continuous proliferation during blood stage infection. Here, we studied the role of heterochromatin protein 1 (HP1), an evolutionary conserved regulator of heritable gene silencing, in the biology of P. falciparum blood stage parasites. We demonstrate that conditional PfHP1 depletion de-represses hundreds of heterochromatic virulence genes and disrupts the elusive mechanism underlying mutually exclusive expression and antigenic variation of PfEMP1. Intriguingly, we also discovered that the PfHP1-dependent regulation of an ApiAP2 transcription factor controls the switch from asexual parasite proliferation to sexual differentiation. This uncovers the first mechanistic insight into the unknown pathway triggering gametocyte conversion and establishes a new concept of HP1-dependent cell fate decision in unicellular eukaryotes. P. falciparum 3D7 parasites expressing endogenous PfHP1-GFP-DD were grown in presence of 4nM WR/625nM Shield-1 (3D7/HP1ON) or 4nM WR (3D7/HP1OFF). RNA extracted from these samples at eleven consecutive time points each was processed for microarray analysis.

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