Expression patterns of Plasmodium falciparum clonally variant genes at the onset of a blood infection in non-immune humans
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PROVIDER: PRJNA699860 | ENA |
REPOSITORIES: ENA
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Project description:Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum parasites to the fluctuating conditions of the human host, but their expression patterns under the natural conditions of the blood circulation have been characterized in detail only for a few specific gene families. Here we provide a detailed characterization of the full P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in non-immune human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occur for CVGs. Specifically, we observed a major increase in the transcript levels of most members of the pfmc-2tm and gbp families and of specific genes of other families, in addition to previously reported changes in var and clag3 genes. The expression patterns were almost identical between parasites obtained from the different volunteers. Large transcriptional differences correlate with changes in the distribution of histone modifications associated with heterochromatin, confirming their epigenetic nature. The analysis of parasites collected at different points along the infection indicates that when parasites pass through transmission stages, the epigenetic memory at CVG loci is lost, resulting in a reset of their expression state and reestablishment of new epigenetic patterns.
2021-07-01 | GSE166258 | GEO
Project description:Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum parasites to the fluctuating conditions of the human host, but their expression patterns under the natural conditions of the blood circulation have been characterized in detail only for a few specific gene families. Here we provide a detailed characterization of the full P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in non-immune human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occur for CVGs. Specifically, we observed a major increase in the transcript levels of most members of the pfmc-2tm and gbp families and of specific genes of other families, in addition to previously reported changes in var and clag3 genes. The expression patterns were almost identical between parasites obtained from the different volunteers. Large transcriptional differences correlate with changes in the distribution of histone modifications associated with heterochromatin, confirming their epigenetic nature. The analysis of parasites collected at different points along the infection indicates that when parasites pass through transmission stages, the epigenetic memory at CVG loci is lost, resulting in a reset of their expression state and reestablishment of new epigenetic patterns.
2021-07-01 | GSE166390 | GEO
Project description:Expression patterns of Plasmodium falciparum clonally variant genes at the onset of a blood infection in non-immune humans [ChIP-seq]
| PRJNA700660 | ENA
Project description:The survival of malaria parasites in the changing human blood environment largely depends on their ability to alter gene expression by epigenetic mechanisms. The active state of Plasmodium falciparum clonally variant genes is associated with euchromatin characterized by the histone mark H3K9ac, whereas the silenced state is characterized by H3K9me3-based heterochromatin. However, the localization of the euchromatin-heterochromatin transitions associated with expression switches in different clonally variant genes has not been characterized. Here we compared the distribution of heterochromatin between subclones of the same genetic background with different patterns of expressed and silenced clonally variant genes to identify at a genome-wide level the patterns associated with the different transcriptional states. We found that de novo heterochromatin formation or complete disruption of a heterochromatin domain are relatively rare events, and in the majority of loci expression switches can be explained by expansion or retraction of heterochromatin. We describe different modalities of heterochromatin changes linked to transcriptional differences, revealing a complex scenario. Despite this complexity, heterochromatin distribution patterns generally enable prediction of the transcriptional state of clonally variant genes. Some subclones expressed and had in an active chromatin state several var genes simultaneously. We also found that heterochromatin levels in the putative regulatory region of the gdv1-as non-coding RNA, previously involved in sexual commitment, varied between parasite lines with different sexual conversion rates.
2022-11-03 | GSE208560 | GEO
Project description:The survival of malaria parasites in the changing human blood environment largely depends on their ability to alter gene expression by epigenetic mechanisms. The active state of Plasmodium falciparum clonally variant genes is associated with euchromatin characterized by the histone mark H3K9ac, whereas the silenced state is characterized by H3K9me3-based heterochromatin. However, the localization of the euchromatin-heterochromatin transitions associated with expression switches in different clonally variant genes has not been characterized. Here we compared the distribution of heterochromatin between subclones of the same genetic background with different patterns of expressed and silenced clonally variant genes to identify at a genome-wide level the patterns associated with the different transcriptional states. We found that de novo heterochromatin formation or complete disruption of a heterochromatin domain are relatively rare events, and in the majority of loci expression switches can be explained by expansion or retraction of heterochromatin. We describe different modalities of heterochromatin changes linked to transcriptional differences, revealing a complex scenario. Despite this complexity, heterochromatin distribution patterns generally enable prediction of the transcriptional state of clonally variant genes. Some subclones expressed and had in an active chromatin state several var genes simultaneously. We also found that heterochromatin levels in the putative regulatory region of the gdv1-as non-coding RNA, previously involved in sexual commitment, varied between parasite lines with different sexual conversion rates. Gene expression data for subclones A7, E5 and B11 (3D7-B stock).
2022-11-03 | GSE208131 | GEO
Project description:Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum to fluctuating conditions of the human host. However, their expression patterns under the natural conditions of the blood circulation have been characterized in detail for only a few specific gene families. Here, we provide a detailed characterization of the complete P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in malaria-naive human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occurred in CVGs. In particular, we observed a major increase in the transcript levels of most genes of the pfmc-2tm and gbp families and of specific genes of other families, such as phist, hyp10, rif, or stevor, in addition to previously reported changes in var and clag3 gene expression. Increased transcript levels of individual pfmc-2tm, rif, and stevor genes involved activation in small subsets of parasites. Large transcriptional differences correlated with changes in the distribution of heterochromatin, confirming their epigenetic nature. Furthermore, the similar expression of several CVGs between parasites collected at different time points along the blood infection suggests that the epigenetic memory for multiple CVG families is lost during transmission stages, resulting in a reset of their transcriptional state. Finally, the CVG expression patterns observed in a volunteer likely infected by a single sporozoite suggest that new epigenetic patterns are established during liver stages. IMPORTANCE The ability of malaria parasites to adapt to changes in the human blood environment, where they produce long-term infection associated with clinical symptoms, is fundamental for their survival. CVGs, regulated at the epigenetic level, play a major role in this adaptive process, as changes in the expression of these genes result in alterations in the antigenic and functional properties of the parasites. However, how these genes are expressed under the natural conditions of the human circulation and how their expression is affected by passage through transmission stages are not well understood. Here, we provide a comprehensive characterization of the expression patterns of these genes at the onset of human blood infections, which reveals major differences with in vitro-cultured parasites. We also show that, during transmission stages, the previous expression patterns for many CVG families are lost, and new patterns are established.
| S-EPMC8406225 | biostudies-literature
Project description:An ApiAP2 member regulates expression of clonally variant genes of the human malaria parasite Plasmodium falciparum
| PRJEB20833 | ENA
Project description:Patterns of heterochromatin distribution alterations linked to transcriptional changes at Plasmodium falciparum clonally variant gene loci
| PRJNA860104 | ENA
Project description:Expression patterns of Plasmodium falciparum clonally variant genes at the onset of a blood infection in non-immune humans
| PRJNA699845 | ENA
Project description:Patterns of heterochromatin distribution alterations linked to transcriptional changes at Plasmodium falciparum clonally variant gene loci [gene expression]
| PRJNA858441 | ENA