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

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

PROVIDER: PRJNA765579 | 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 [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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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.

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