Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1222616 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Malaria pathogenesis, encompassing parasite invasion, egress, and antigenic variation, relies on the coordinated activity of numerous proteins, yet their molecular regulatory mechanisms remain poorly understood. Here, we define the role of PfAP2-V, a critical AP2 transcription factor in Plasmodium falciparum, during intra-erythrocytic developmental cycle. PfAP2-V displayed two distinct peaks of expression and was critical for parasite proliferation, invasion, and the regulation of virulence-associated genes. Inducible knockdown of PfAP2-V reduced parasitemia by blocking trophozoite development, which was associated with downregulated phosphorylation of virulence-associated proteins. Furthermore, PfAP2-V knockdown reduced PfEMP1 expression, impairing the adhesion of infected red blood cells to endothelial receptors. Genome-wide chromosome conformation capture and chromatin immunoprecipitation sequencing analyses revealed that PfAP2-V knockdown altered chromatin interactions and accessibility, disrupting the regulation of antigenic variant genes. These findings establish PfAP2-V as a key transcriptional regulator at distinct stages of the intra-erythrocytic cycle.
2025-03-25 | GSE288146 | GEO
Project description:The Plasmodium falciparum ApiAP2 transcription factor PfAP2-V controls parasite proliferation and virulence in intra-erythrocytic developmental cycle
| PRJNA1216279 | ENA
Project description:The lack of a comprehensive map of transcription start sites (TSS) across P. falciparum genome has hampered advances in decrypting the molecular mechanisms underlying regulation of gene expression in the malaria parasite. In eukaryotic model organisms, development of genome-wide approaches and next-generation sequencing technologies has contributed to a better understanding of the impact of local nucleotide composition on transcriptional regulation. Using such methods, we generated a single nucleotide-resolution map of transcription initiation events during P. falciparum intra-erythrocytic developmental cycle. Examination of transcription start site during the intra-erythorcytic development of the human parasite Plasmodium falciparum
2016-03-02 | E-GEOD-68982 | biostudies-arrayexpress
Project description:Transcriptional profiling of transgenic P. falciparum asexual blood stage parasites of the transgenic strain 3D7/DDGFP-PfAP2-HC at five time points during intra-erythrocytic parasite development. The DD (FKBP destabilisation domain) allows for the conditional expression of fusion proteins: DD fusion proteins are rapidly degraded or stably expressed in absence or presence of the stabilising ligand Shield-1, respectively (Banaszynski LA, Chen LC, Maynard-Smith LA, Ooi AG, Wandless TJ. A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules.Cell. 2006 Sep 8;126(5):995-1004). The goal of this experiment was to identify genes differentially expressed in DDGFP-PfAP2-HC-expressing compared to DDGFP-PfAP2-HC-depleted parasites during the intra-erythtrocytic cell cycle.
2020-10-06 | GSE159061 | GEO
Project description:Obligate intracellular parasites must efficiently invade host cells in order to mature and be transmitted. For the malaria parasite Plasmodium falciparum, invasion of host red blood cells (RBCs) is essential. Here we describe a parasite-specific transcription factor belonging to the Apicomplexan Apetala 2 (ApiAP2) family that is responsible for regulating the expression of a subset of merozoite genes involved in RBC invasion (PfAP2-I). Our genome-wide analysis by ChIP-seq shows that PfAP2-I interacts with a specific DNA motif in the promoters of these genes. msp5 transcription levels decrease when the PfAP2-I DNA-binding motif is mutated in PfAP2-I-GFP parasites, showing that PfAP2-I must bind the DNA motif in order for msp5 to be transcribed.
2016-12-31 | GSE77809 | GEO
Project description:Obligate intracellular parasites must efficiently invade host cells in order to mature and be transmitted. For the malaria parasite Plasmodium falciparum, invasion of host red blood cells (RBCs) is essential. Here we describe a parasite-specific transcription factor belonging to the Apicomplexan Apetala 2 (ApiAP2) family that is responsible for regulating the expression of a subset of merozoite genes involved in RBC invasion (PfAP2-I). Our genome-wide analysis by ChIP-seq shows that PfAP2-I interacts with a specific DNA motif in the promoters of these genes. msp5 transcription levels decrease when the PfAP2-I DNA-binding motif is mutated in PfAP2-I-GFP parasites, showing that PfAP2-I must bind the DNA motif in order for msp5 to be transcribed.
2016-12-31 | GSE77807 | GEO
Project description:Differentiation from asexual blood stages to sexual gametocytes is required for transmission of malaria parasites from the human to the mosquito host. Preventing gametocyte commitment and development would block parasite transmission, but the underlying molecular mechanisms behind these processes remain poorly understood. Here, we report that the ApiAP2 transcription factor, PfAP2-G2 (PF3D7_1408200) plays a critical role in the maturation of Plasmodium falciparum gametocytes. PfAP2-G2 binds to the promoters of a wide array of genes that are expressed at many stages of the parasite life cycle. Interestingly, we also find binding of PfAP2-G2 within the gene body of almost 3000 genes, which strongly correlates with the location of H3K36me3 and several other histone modifications as well as Heterochromatin Protein 1 (HP1), suggesting that occupancy of PfAP2-G2 in gene bodies may serve as an alternative regulatory mechanism. Disruption of pfap2-g2 does not impact asexual development, parasite multiplication rate, or commitment to sexual development but the majority of sexual parasites are unable to mature beyond stage III gametocytes. The absence of pfap2-g2 leads to overexpression of 28% of the genes bound by PfAP2-G2 and none of the PfAP2-g2 bound are downregulated, suggesting that it is a repressor. We also find that PfAP2-G2 interacts with chromatin remodeling proteins, a microrchidia (MORC) protein, and another ApiAP2 protein (PF3D7_1139300). Overall our data demonstrate that PfAP2-G2 is an important transcription factor that establishes an essential gametocyte maturation program in association with other chromatin-related proteins.
2021-02-01 | GSE160924 | GEO
Project description:Differentiation from asexual blood stages to sexual gametocytes is required for transmission of malaria parasites from the human to the mosquito host. Preventing gametocyte commitment and development would block parasite transmission, but the underlying molecular mechanisms behind these processes remain poorly understood. Here, we report that the ApiAP2 transcription factor, PfAP2-G2 (PF3D7_1408200) plays a critical role in the maturation of Plasmodium falciparum gametocytes. PfAP2-G2 binds to the promoters of a wide array of genes that are expressed at many stages of the parasite life cycle. Interestingly, we also find binding of PfAP2-G2 within the gene body of almost 3000 genes, which strongly correlates with the location of H3K36me3 and several other histone modifications as well as Heterochromatin Protein 1 (HP1), suggesting that occupancy of PfAP2-G2 in gene bodies may serve as an alternative regulatory mechanism. Disruption of pfap2-g2 does not impact asexual development, parasite multiplication rate, or commitment to sexual development but the majority of sexual parasites are unable to mature beyond stage III gametocytes. The absence of pfap2-g2 leads to overexpression of 28% of the genes bound by PfAP2-G2 and none of the PfAP2-g2 bound are downregulated, suggesting that it is a repressor. We also find that PfAP2-G2 interacts with chromatin remodeling proteins, a microrchidia (MORC) protein, and another ApiAP2 protein (PF3D7_1139300). Overall our data demonstrate that PfAP2-G2 is an important transcription factor that establishes an essential gametocyte maturation program in association with other chromatin-related proteins.
2021-02-01 | GSE160923 | GEO
Project description:Investigations on the fundamental of malaria parasite biology, such as invasion, growth cycle, metabolism and cell signalling have uncovered a number of potential antimalarial drug targets, including choline kinase, a key enzyme involved in the synthesis of phosphatidylcholine, an important component in parasite membrane compartment. The effect on gene expression of Plasmodium falciparum K1 strain following 72 hours exposure to 2 μM (IC50 concentration) of the choline kinase inhibitor, hexadecyltrimethylammonium bromide (HDTAB) was evaluated by DNA microarray analysis. Genes important in P. falciparum intra-erythrocytic life cycle, such as invasion, cytoadherance and growth were among those affected by at least 2-fold changes in their expression levels compared with non HDTAB-treated control.
2014-02-08 | GSE54775 | GEO
Project description:Investigations on the fundamental of malaria parasite biology, such as invasion, growth cycle, metabolism and cell signalling have uncovered a number of potential antimalarial drug targets, including choline kinase, a key enzyme involved in the synthesis of phosphatidylcholine, an important component in parasite membrane compartment. The effect on gene expression of Plasmodium falciparum K1 strain following 72 hours exposure to 2 M-NM-<M (IC50 concentration) of the choline kinase inhibitor, hexadecyltrimethylammonium bromide (HDTAB) was evaluated by DNA microarray analysis. Genes important in P. falciparum intra-erythrocytic life cycle, such as invasion, cytoadherance and growth were among those affected by at least 2-fold changes in their expression levels compared with non HDTAB-treated control. Two different cultures of P. falciparum was divided into two groups, untreated and HDTAB treated. The parasites were incubated for 72 hours and harvested for total RNA extraction. The expression profile was analysed by microarray.
2014-02-08 | E-GEOD-54775 | biostudies-arrayexpress