Plasmodium falciparum
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA145129 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The P. falciparum genome is equipped with several subtelomeric gene families that are implicated in parasite virulence and immune evasion. The members of these gene families are uniformly positioned within heterochromatic domains of the genome and are thus subject to variegated expression. The best-studied example is that of the var gene family encoding the major parasite virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). Transcriptional regulation of other subtelomeric gene families and their role in parasite biology is much less understood. Here, we investigated the mode of transcriptional control of var, rif, stevor, phist and pfmc-2tm families by comparative genome-wide transcriptional profiling of transgenic parasite lines. Our results establish a clear functional distinction between var and non-var transcriptional control mechanisms. Unlike var promoters, we find that promoters of non-var families are not silenced by default. Moreover, we show that mutually exclusive transcription is unique to the var gene family.
2011-09-02 | GSE31829 | GEO
Project description:The process of erythrocyte invasion by merozoites of Plasmodium falciparum involves multiple steps, including the formation of a moving junction characterized by the redundancy of many of the receptor-ligand interactions involved. Several of the parasite proteins that interact with erythrocyte receptors or participate in other steps of the process of invasion are encoded by small subtelomerically-located multigene families of four to seven members. We report here that members of the multigene families pfRh, eba, rhopH1/clag and acbp exist in either an active or a silenced state. In the case of two members of the rhopH1/clag family, clag3.1 and clag3.2, expression was mutually exclusive. Silencing occurred in the absence of detectable DNA alterations, suggesting that it is transmitted epigenetically. This was unambiguously demonstrated for eba-140, which was silenced by the formation of facultative heterochromatin. Our data demonstrate that variant expression, epigenetic silencing and mutually exclusive expression in Plasmodium are not unique to genes encoding proteins exported to the surface of the erythrocyte like var genes but also occur for genes involved in host cell invasion..
2007-11-26 | E-SGRP-9 | biostudies-arrayexpress
Project description:The P. falciparum genome is equipped with several subtelomeric gene families that are implicated in parasite virulence and immune evasion. The members of these gene families are uniformly positioned within heterochromatic domains of the genome and are thus subject to variegated expression. The best-studied example is that of the var gene family encoding the major parasite virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). Transcriptional regulation of other subtelomeric gene families and their role in parasite biology is much less understood. Here, we investigated the mode of transcriptional control of var, rif, stevor, phist and pfmc-2tm families by comparative genome-wide transcriptional profiling of transgenic parasite lines. Our results establish a clear functional distinction between var and non-var transcriptional control mechanisms. Unlike var promoters, we find that promoters of non-var families are not silenced by default. Moreover, we show that mutually exclusive transcription is unique to the var gene family. 3D7 wild-type parasites were transfected with constructs carrying eight different promoters that drive expression of the drug-selectable marker hdhfr-gfp. Thereof seven promoters are members of the multigene families upsA var, upsB var, upsC var, rif, stevor, phistb and pfmc-2tm. The cam promoter was used as transfection-based control and also a wild-type 3D7 cell line was included as control. These nine cell lines were subjected to genome-wide transcriptional profiling. Parasites were synchronized to obtain an 8 hour growth window and were harvested at four consecutive timepoints (TP): TP1 (6-14 hours post-invasion (hpi)); TP2 (14-22 hpi); TP3 (22-30 hpi); TP4 (30-38 hpi) to monitor intra- and inter-family specific linkage of multigene family expression.
2011-09-01 | E-GEOD-31829 | biostudies-arrayexpress
Project description:The mutually exclusive expression of virulence genes is critical for the immune evasion and pathogenesis of malaria parasites, Plasmodium falciparum, in human host. The three-dimensional genome structure has emerged as a new factor involved in transcriptional regulation of virulence gene families in the parasites. However, the mechanism controlling this epigenetic regulation pathway remains elusive. Here, we have identified the highly conserved high mobility group protein HMGB1 as a critical architectural regulator in establishment of high-order genome structure via interaction with centromeres in P. falciparum. Genetic manipulation of Pfhmgb1 gene and Hi-C analysis showed that the boundary of telomere and centromere clusters in an opposite spatial relationship in the nucleus was disrupted upon hmgb1 knockout. The collapse of euchromatic centromere cluster from nuclear periphery towards the opposite heterochromatic telomere cluster triggered relocation of the original active var gene, which resulted in complete silence of the entire repertoire of var gene family. ChIP-seq and fluorescence assay analysis confirmed the specific interaction between PfHMGB1 and centromeres. Meanwhile, as in other eukaryotes, PfHMGB1 was also widely present on the promoter regions of a variety of genes and co-regulated transcription, including other non-var variant gene families, suggesting multiple dimensions of epigenetic gene regulation by PfHMGB1. Finally, the natural genome organization could be reconstructed by hmgb1 gene complementation, which rescued the mutually exclusive expression of virulence genes. Taken together, our work provides new insight into the evolution of biological functions of the HMG architectural superfamily in eukaryotes.
2021-04-14 | GSE141759 | GEO
Project description:The mutually exclusive expression of virulence genes is critical for the immune evasion and pathogenesis of malaria parasites, Plasmodium falciparum, in human host. The three-dimensional genome structure has emerged as a new factor involved in transcriptional regulation of virulence gene families in the parasites. However, the mechanism controlling this epigenetic regulation pathway remains elusive. Here, we have identified the highly conserved high mobility group protein HMGB1 as a critical architectural regulator in establishment of high-order genome structure via interaction with centromeres in P. falciparum. Genetic manipulation of Pfhmgb1 gene and Hi-C analysis showed that the boundary of telomere and centromere clusters in an opposite spatial relationship in the nucleus was disrupted upon hmgb1 knockout. The collapse of euchromatic centromere cluster from nuclear periphery towards the opposite heterochromatic telomere cluster triggered relocation of the original active var gene, which resulted in complete silence of the entire repertoire of var gene family. ChIP-seq and fluorescence assay analysis confirmed the specific interaction between PfHMGB1 and centromeres. Meanwhile, as in other eukaryotes, PfHMGB1 was also widely present on the promoter regions of a variety of genes and co-regulated transcription, including other non-var variant gene families, suggesting multiple dimensions of epigenetic gene regulation by PfHMGB1. Finally, the natural genome organization could be reconstructed by hmgb1 gene complementation, which rescued the mutually exclusive expression of virulence genes. Taken together, our work provides new insight into the evolution of biological functions of the HMG architectural superfamily in eukaryotes.
2021-04-14 | GSE141761 | GEO
Project description:The mutually exclusive expression of virulence genes is critical for the immune evasion and pathogenesis of malaria parasites, Plasmodium falciparum, in human host. The three-dimensional genome structure has emerged as a new factor involved in transcriptional regulation of virulence gene families in the parasites. However, the mechanism controlling this epigenetic regulation pathway remains elusive. Here, we have identified the highly conserved high mobility group protein HMGB1 as a critical architectural regulator in establishment of high-order genome structure via interaction with centromeres in P. falciparum. Genetic manipulation of Pfhmgb1 gene and Hi-C analysis showed that the boundary of telomere and centromere clusters in an opposite spatial relationship in the nucleus was disrupted upon hmgb1 knockout. The collapse of euchromatic centromere cluster from nuclear periphery towards the opposite heterochromatic telomere cluster triggered relocation of the original active var gene, which resulted in complete silence of the entire repertoire of var gene family. ChIP-seq and fluorescence assay analysis confirmed the specific interaction between PfHMGB1 and centromeres. Meanwhile, as in other eukaryotes, PfHMGB1 was also widely present on the promoter regions of a variety of genes and co-regulated transcription, including other non-var variant gene families, suggesting multiple dimensions of epigenetic gene regulation by PfHMGB1. Finally, the natural genome organization could be reconstructed by hmgb1 gene complementation, which rescued the mutually exclusive expression of virulence genes. Taken together, our work provides new insight into the evolution of biological functions of the HMG architectural superfamily in eukaryotes.
2021-04-14 | GSE141760 | GEO
Project description:The mutually exclusive expression of virulence genes is critical for the immune evasion and pathogenesis of malaria parasites, Plasmodium falciparum, in human host. The three-dimensional genome structure has emerged as a new factor involved in transcriptional regulation of virulence gene families in the parasites. However, the mechanism controlling this epigenetic regulation pathway remains elusive. Here, we have identified the highly conserved high mobility group protein HMGB1 as a critical architectural regulator in establishment of high-order genome structure via interaction with centromeres in P. falciparum. Genetic manipulation of Pfhmgb1 gene and Hi-C analysis showed that the boundary of telomere and centromere clusters in an opposite spatial relationship in the nucleus was disrupted upon hmgb1 knockout. The collapse of euchromatic centromere cluster from nuclear periphery towards the opposite heterochromatic telomere cluster triggered relocation of the original active var gene, which resulted in complete silence of the entire repertoire of var gene family. ChIP-seq and fluorescence assay analysis confirmed the specific interaction between PfHMGB1 and centromeres. Meanwhile, as in other eukaryotes, PfHMGB1 was also widely present on the promoter regions of a variety of genes and co-regulated transcription, including other non-var variant gene families, suggesting multiple dimensions of epigenetic gene regulation by PfHMGB1. Finally, the natural genome organization could be reconstructed by hmgb1 gene complementation, which rescued the mutually exclusive expression of virulence genes. Taken together, our work provides new insight into the evolution of biological functions of the HMG architectural superfamily in eukaryotes.
2021-04-14 | GSE141758 | GEO
Project description:Dynamic control of gene expression is critical for blood stage development of malaria parasites. Here, we used multi-omic analyses to investigate transcriptional regulation by the chromatin-associated microrchidia protein, PfMORC, during asexual blood stage development of the human malaria parasite Plasmodium falciparum. PfMORC (PF3D7_1468100) interacts with a suite of nuclear proteins, including APETALA2 (AP2) transcription factors (PfAP2-G5, PfAP2-O5, PfAP2-I, PfAP2-MRP and PF3D7_0420300, PF3D7_0613800, and PF3D7_1239200), a DNA helicase DS60 (PF3D7_1227100), and other chromatin remodelers (PfCHD1, PfEELM2, and PfISWI). Transcriptomic analysis of PfMORCHA-glmS knockdown parasites revealed 163 differentially expressed genes belonging to hypervariable multigene families, along with upregulation of genes mostly involved in host cell invasion. In vivo genome-wide chromatin occupancy analysis during both trophozoite and schizont stages of development demonstrates that PfMORC is recruited to repressed, multigene families, including the var genes in subtelomeric chromosomal regions. Collectively, we find that PfMORC is found in chromatin complexes that play a role in the epigenetic control of asexual blood stage transcriptional regulation.
2024-11-05 | GSE239393 | GEO
Project description:The malaria parasite Plasmodium falciparum employs antigenic variation of the virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1) to escape adaptive immune responses during blood infection. Antigenic variation of PfEMP1 occurs through transcriptional switches in the mutually exclusive expression of individual members of the multi-copy var gene family. var genes are located in perinuclear clusters of transcriptionally inactive heterochromatin. Singular var gene activation is linked to locus repositioning into a dedicated zone at the nuclear periphery and deposition of histone 3 lysine 4 di-/trimethylation (H3K4me2/3) and H3K9 acetylation marks in the promoter region. While previous work identified the putative H3K4-specific methyltransferase PfSET10 as an essential enzyme and positive regulator of var gene expression, a recent study reported conflicting data. Here, we used iterative genome editing to engineer a conditional PfSET10 knockout line tailored to study the function of PfSET10 in var gene regulation. We demonstrate that PfSET10 is not required for mutually exclusive var gene expression and switching. We also show that PfSET10 is dispensable not only for asexual parasite proliferation but also for sexual conversion and differentiation of gametocytes. Furthermore, comparative RNA-seq experiments revealed that PfSET10 plays no obvious role in regulating gene expression during asexual parasite development and gametocytogenesis. Interestingly, however, PfSET10 shows different subnuclear localization patterns in asexual and sexual stage parasites and female-specific expression in mature gametocytes. In summary, our work confirms in detail that PfSET10 is not involved in regulating var gene expression and is not required for blood stage parasite viability, at least not when cultured in vitro, thus suggesting PfSET10 may be important for life cycle progression in the mosquito vector or during liver stage development.
2024-06-26 | GSE270631 | GEO
Project description:Epigenetic processes are the main conductors of phenotypic variation in eukaryotes. The malaria parasite Plasmodium falciparum employs antigenic variation of the major surface antigen PfEMP1, encoded by 60 var genes, to evade acquired immune responses. PfEMP1 also mediates sequestration of infected erythrocytes in the microvasculature, which is directly linked to severe malaria outcomes. Antigenic variation of PfEMP1 occurs through in situ switches in mono-allelic var gene transcription, which is PfSIR2-dependent and associated with the presence of repressive H3K9me3 marks at silenced loci. Here, we show that the P. falciparum ortholog of heterochromatin protein 1 (PfHP1) binds to H3K9me3 and constitutes a major component of heterochromatin in perinuclear chromosome end clusters. High-resolution genome-wide chromatin immuno-precipitation demonstrates the striking association of PfHP1 with non-syntenic virulence gene arrays in subtelomeric and chromosome-internal islands. These include not only var genes but the majority of P. falciparum lineage-specific gene families coding for exported proteins involved in host-parasite interactions. Over-expression of PfHP1 resulted in decreased expression of a small number of (virulance) genes and indicated the presence of well-defined heterochromatic boundaries.. In summary, we uncover an unprecedented function of HP1 as a mayor regulator of virulence gene silencing and phenotypic variation, which will be instrumental for our understanding of this widely used survival strategy of unicellular pathogens.
2009-09-03 | GSE17029 | GEO