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Identification of AP2-O targets

ABSTRACT: Identification of AP2-O targets

PROVIDER: PRJNA252935 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1422090.fastq.gz	Fastqsanger.gz
	SRR1422094.fastq.gz	Fastqsanger.gz
	SRR1422095.fastq.gz	Fastqsanger.gz
	SRR1422096.fastq.gz	Fastqsanger.gz
	SRR1422097.fastq.gz	Fastqsanger.gz

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Identification of AP2-O targets [microarray]

Project description:Stage-specific transcription is a fundamental biological process in the lifecycle of the Plasmodium parasite. Proteins containing the AP2 DNA-binding domain are responsible for stage-specific transcriptional regulation, and belong to the only known family of transcription factors in Plasmodium parasites. A comprehensive identification of their target genes will advance our understanding of the molecular basis of stage-specific parasite development. In this study, we have used ChIP-seq technology to identify the target genes of the ookinete-specific AP2 transcription factor AP2-O.

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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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Project description:AP2-FG is a female-specific transcription factor (TF) that plays an essential role in female gametocyte development. AP2-FG activates hundreds of genes by binding to a female-specific ten-base cis-acting element. Here, we report that in the rodent malaria parasite Plasmodium berghei, another female-specific TF designated as a partner of AP2-FG (PFG), controls gene expression in female gametocytes cooperatively with AP2-FG. Transcriptional mechanisms were analyzed in Plasmodium berghei female gametocytes.

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Induction of target genes of AP2-Sp in AP2-O::Sp parasites

Project description:Sporozoite-specific genes were induced in parasites that express AP2-O whose AP2 domain was swapped with that of AP2-Sp. DNA construct encoding AP2 domain of AP2-Sp was introduced into P. bergei schizonts. It was integrated into the locus of the endogenious AP2-O gene, resulting in swap of the AP2-domain (AP2-O::Sp parasites). Gene expression was analyzed in ookinetes cultured for 20h.

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Project description:Sporozoite-specific genes were induced in parasites that express AP2-O whose AP2 domain was swapped with that of AP2-Sp.

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RNAseq experiment to identify differentially expressed genes by AP2 induction in the Shoot Apical Meristem (SAM) of Arabidopsis

Project description:Trough a two components inducible system, we expressed ectopically in the SAM a resistant version of AP2 to the regulation of miR172 (AP2m3). The differentially expressed genes by AP2 induction allows the identification of differents groups of genes that could mediate AP2 functions in the SAM.

2020-10-20 | GSE151082 | GEO

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