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

ABSTRACT: 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.

ORGANISM(S): Plasmodium berghei

SUBMITTER: Masao Yuda

PROVIDER: E-GEOD-18910 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcription factor AP2-Sp and its target genes in malarial sporozoites.

Yuda Masao M Iwanaga Shiroh S Shigenobu Shuji S Kato Tomomi T Kaneko Izumi I

Molecular microbiology 20091216 4

The malarial sporozoite is the stage that infects the liver, and genes expressed in this stage are potential targets for vaccine development. Here, we demonstrate that specific gene expression in this stage is regulated by an AP2-related transcription factor, designated AP2-Sp (APETALA2 in sporozoites), that is expressed from the late oocyst to the salivary gland sporozoite. Disruption of the AP2-Sp gene did not affect parasite replication in the erythrocyte but resulted in loss of sporozoite fo ...[more]

PMID: 20025671

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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.

2009-11-09 | GSE18910 | GEO

Comparison of gene expression between wild type and AP2-L KO parasites

Project description:In the rodent malaria parasite Plasmodium berghei, we found that an AP2 family transcription factor designated AP2-L plays a critical role in the development of the liver stage. Using DNA microarray analysis we showed that the expression of several genes, including those of parasitophorous vacuole membrane proteins, was significantly decreased in the early liver stage of AP2-L-depleted parasites. Gene expression of P. berghei liver stages was compared between wild type and AP2-L KO parasites. Liver stage parasites were cultured for 24h using HepG2 cells. Ten and seven biologically independent experiments were performed for wild type and AP2-L KO parasites, respectively.

2012-04-30 | E-GEOD-34877 | biostudies-arrayexpress

Comparison of gene expression between wild type and AP2-G KO parasites.

Project description:In the rodent malaria parasite Plasmodium berghei, we found that an AP2 family transcription factor designated AP2-L plays a critical role in the development of the liver stage. Using DNA microarray analysis we showed that the expression of several genes, including those of parasitophorous vacuole membrane proteins, was significantly decreased in the early liver stage of AP2-L-depleted parasites. Gene expression of P. berghei sporozoites was compared between wild type and AP2-G KO parasites. Five biologically independent experiments were performed for each genotype.

2012-04-30 | E-GEOD-34806 | biostudies-arrayexpress

Differential gene expression in ap2-g and ap2-g2 mutants of Plasmodium berghei

Project description:Commitment to and completion of sexual development are essential for malaria parasites to be transmitted through mosquitoes. The molecular mechanism(s) responsible for these processes however, remain largely unknown. We have identified two transcription factors (both belonging to the AP2 family) essential for gametocytogenesis. AP2-G mutants are characterised by a complete inability to produce gametocytes. In AP2-G2 mutants the gametocytaemia is very significantly reduced but not completely abolished. We have performed the microarray experiments in order to cokmpare the transcriptomes of these mutantnts to the WT parasites and between each other. As P.berghei parasites are characterised by asynchronous development in the rodent host, the different stage composition of the sample would impact the analysis. Therefore parasites were harvested and matured in in vitro to the schizont stage Pairwaise comparison between the mutants and parental line was performed. 3 biological replicates of each condition were used.

2013-12-03 | E-GEOD-52859 | biostudies-arrayexpress

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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Identification of AP2-O targets [RNA-Seq]

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Identification of AP2-O targets [ChIP-seq II]

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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

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