PfAP2-G ChIP-seq in committed schizonts, sexual rings, and stage I gametocytes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA493084 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7903650.fastq.gz | Fastqsanger.gz | |||
| SRR7903651.fastq.gz | Fastqsanger.gz | |||
| SRR7903652.fastq.gz | Fastqsanger.gz | |||
| SRR7903653.fastq.gz | Fastqsanger.gz | |||
| SRR7903654.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:In the malaria parasite Plasmodium falciparum, the switch from asexual multiplication to sexual differentiation into gametocytes is essential for transmission to mosquitos. One of the key determinants of sexual commitment is the transcription factor PfAP2-G, which has been proposed to orchestrate this crucial cell fate decision by driving expression of gametocyte genes. We show conclusively that PfAP2-G is a transcriptional activator of gametocyte genes and identify the earliest known markers expressed during commitment. Remarkably, we also find that in sexually committed cells, PfAP2-G is associated with the promoters of genes important for red blood cell invasion and activates them through its interactions with a second transcription factor. We thus demonstrate an intriguing transcriptional link between the apparently opposing processes of red blood cell invasion and gametocytogenesis that is coordinated by the master regulator PfAP2-G. This finding has important implications for the development of new anti-malarial drugs that block the invasion of red blood cells by sexually committed cells, thereby preventing parasite transmission.
2019-02-11 | GSE120448 | GEO
Project description:Malaria transmission requires the conversion of some asexual parasites into sexual forms termed gametocytes. The initial stages of sexual development, including sexually-committed schizonts and sexual rings, remain poorly characterized, in part because only a subset of parasites undergo sexual development and they are morphologically identical to their asexual counterparts. Here we present a system based on conditional expression of PfAP2-G, the master regulator of sexual conversion, for controlled sexual induction. Induction resulted in ~90% sexual conversion, which enables the characterization of early sexual stages without further purification. Transcriptomic analysis identified the alterations that follow pfap2-g activation, including identification of genes that are down-regulated. We also show that the inducible system enables the characterization of committed stages at the phenotypic level. Altogether, the inducible lines will facilitate the study of the initial stages of sexual development, which is important for the development of new strategies to stop malaria transmission.
2020-06-10 | GSE135005 | GEO
Project description:Malaria transmission requires the conversion of some asexual parasites into sexual forms termed gametocytes. The initial stages of sexual development, including sexually-committed schizonts and sexual rings, remain poorly characterized, in part because only a subset of parasites undergo sexual development and they are morphologically identical to their asexual counterparts. Here we present a system based on conditional expression of PfAP2-G, the master regulator of sexual conversion, for controlled sexual induction. Induction resulted in ~90% sexual conversion, which enables the characterization of early sexual stages without further purification. Transcriptomic analysis identified the alterations that follow pfap2-g activation, including identification of genes that are down-regulated. We also show that the inducible system enables the characterization of committed stages at the phenotypic level. Altogether, the inducible lines will facilitate the study of the initial stages of sexual development, which is important for the development of new strategies to stop malaria transmission.
2020-06-10 | GSE135002 | GEO
Project description:PfAP2-G and PfAP2-I ChIP-seq in schizonts
| PRJNA493135 | ENA
Project description:In the malaria parasite Plasmodium falciparum, the switch from asexual multiplication to sexual differentiation into gametocytes is essential for transmission to mosquitos. One of the key determinants of sexual commitment is the transcription factor PfAP2-G, which has been proposed to orchestrate this crucial cell fate decision by driving expression of gametocyte genes. Here we identify for the first time the direct targets of PfAP2-G and demonstrate that it dynamically binds hundreds of sites across the genome. We also identify major differences in PfAP2-G occupancy between gametocytes derived via next-cycle and same-cycle conversion, suggesting significant biological differences between these two pathways. By using a combination of ChIP-seq, transcriptomics, and CRISPR-Cas9, we are able to show definitively that PfAP2-G is a transcriptional activator of early gametocyte genes. Our data implicate PfAP2-G not just as a transcriptional activator of gametocyte genes, but also as a regulator of genes important for red blood cell invasion. Excitingly, we also demonstrate that PfAP2-G interacts with a second transcription factor to regulate transcription. These results shed new light on a critical part of the malaria parasite lifecycle by clarifying the role of PfAP2-G during gametocytogenesis.
2019-07-17 | GSE134268 | GEO
Project description:In the malaria parasite Plasmodium falciparum, the switch that occurs from asexual multiplication to sexual differentiation is essential for transmission to mosquitos. One of the key drivers of commitment to sexual development is the transcription factor AP2-G. Although it has been hypothesised that AP2-G orchestrates this crucial cell fate decision by driving expression of gametocyte genes, the molecular mechanisms by which this occurs remain unknown. We show conclusively that AP2-G is a transcriptional activator of gametocyte genes and identify the earliest target genes expressed during commitment. Remarkably, we also find that in committed cells AP2-G is associated with the promoters of genes important for red blood cell invasion and activates them through its interactions with another transcription factor. We thus demonstrate for the first time an intriguing transcriptional link between the apparently opposing processes of red blood cell invasion and gametocytogenesis. This suggests that committed schizonts may have a distinct invasion preference or pathway that is transcriptionally regulated by AP2-G.
2019-02-11 | GSE120488 | GEO
Project description:In the malaria parasite Plasmodium falciparum, the switch from asexual multiplication to sexual differentiation into gametocytes is essential for transmission to mosquitos. One of the key determinants of sexual commitment is the transcription factor PfAP2-G, which has been proposed to orchestrate this crucial cell fate decision by driving expression of gametocyte genes. We show conclusively that PfAP2-G is a transcriptional activator of gametocyte genes and identify the earliest known markers expressed during commitment. Remarkably, we also find that in sexually committed cells, PfAP2-G is associated with the promoters of genes important for red blood cell invasion and activates them through its interactions with a second transcription factor. We thus demonstrate an intriguing transcriptional link between the apparently opposing processes of red blood cell invasion and gametocytogenesis that is coordinated by the master regulator PfAP2-G. This finding has important implications for the development of new anti-malarial drugs that block the invasion of red blood cells by sexually committed cells, thereby preventing parasite transmission.
2019-02-08 | GSE121312 | GEO
Project description:In the malaria parasite Plasmodium falciparum, the switch from asexual multiplication to sexual differentiation into gametocytes is essential for transmission to mosquitos. One of the key determinants of sexual commitment is the transcription factor PfAP2-G, which has been proposed to orchestrate this crucial cell fate decision by driving expression of gametocyte genes. We show conclusively that PfAP2-G is a transcriptional activator of gametocyte genes and identify the earliest known markers expressed during commitment. Remarkably, we also find that in sexually committed cells, PfAP2-G is associated with the promoters of genes important for red blood cell invasion and activates them through its interactions with a second transcription factor. We thus demonstrate an intriguing transcriptional link between the apparently opposing processes of red blood cell invasion and gametocytogenesis that is coordinated by the master regulator PfAP2-G. This finding has important implications for the development of new anti-malarial drugs that block the invasion of red blood cells by sexually committed cells, thereby preventing parasite transmission.
2019-02-08 | GSE120990 | 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