Plasmodium falciparum
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ABSTRACT:
PROVIDER: PRJNA630836 | ENA |
REPOSITORIES: ENA
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Project description:The variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), expressed on the surface of P. falciparum infected Red Blood Cells (iRBCs) is a critical virulence factor for malaria. Each parasite encodes 60 antigenically distinct var genes encoding PfEMP1s, but during infection the clonal parasite population expresses only one gene at a time before switching to the expression of a new variant antigen as an immune evasion mechanism to avoid the host’s antibody responses. The mechanism by which 59 of the 60 var genes are silenced remains largely unknown. We used microarrays to detail the global programme changes of gene expression caused by each gene knockout with a particular view towards which gene knockout results in transcriptional upregulation of the entire var gene family.
2013-05-25 | GSE47349 | GEO
Project description:We performed Hi-C assay to address the interaction of central var genes in ruf6-var pairs，subtelomeric upsA-subtype var genes and other HP1-associated genes
2020-01-01 | GSE133240 | GEO
Project description:The variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), expressed on the surface of P. falciparum infected Red Blood Cells (iRBCs) is a critical virulence factor for malaria. Each parasite encodes 60 antigenically distinct var genes encoding PfEMP1s, but during infection the clonal parasite population expresses only one gene at a time before switching to the expression of a new variant antigen as an immune evasion mechanism to avoid the hostM-bM-^@M-^Ys antibody responses. The mechanism by which 59 of the 60 var genes are silenced remains largely unknown. We used microarrays to detail the global programme changes of gene expression caused by each gene knockout with a particular view towards which gene knockout results in transcriptional upregulation of the entire var gene family. Plasmodium falciparum clones, in each of which one of different histone lysine methylation modification enzyme genes was knocked out, were synchronized in the asexual stage and collected at indicated time points post invasion of erythrocytes for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify the key epigenetic enzyme that controls silencing of the whole var gene family.
2013-05-25 | E-GEOD-47349 | biostudies-arrayexpress
Project description:P. falciparum undergoes antigenic variation during its life cycle in the human host. To accomplish this, the malaria parasite has developed mechanisms that ensure the expression of a single member of the var gene family to produce one of the PfEMP1 variant proteins. Here we carry out RNA-seq and ChIP-seq analyses of histone modifications to explore transcriptional and epigenomic changes taking place between the transmissible stages of the parasite i.e. gametocytes present in human blood and sporozoites present in the mosquito salivary glands. We find that most var genes are expressed at low levels in gametocytes but a single var gene is selected during the oocyst stage in the mosquito. Clonal expression of a specific var gene is accompanied by the establishment of specific histone modification patterns in the active and inactive genes. These modifications are epigenetically transmitted from the oocyst to the infective sporozoite stage, where expression of the active var gene is amplified by the transcription of an antisense lncRNA. The findings suggest a critical role for the mosquito immune system in determining the choice of var gene activation prior to transmission to the human host.
2017-01-18 | GSE68667 | GEO
Project description:Malaria caused by Plasmodium falciparum involves antigenic variation on the infected red blood cells through mutually exclusive expression of var genes. The repressed var genes have a distinct genome organization where they localize as a cluster near the nuclear periphery and are bound by PfHP1 (P. falciparum Heterochromatin Protein 1). However, the mode of regulation of var genes by PfHP1 remains unclear. In this study, we show that PfHP1 undergoes liquid-liquid phase separation (LLPS) in vitro in an RNA and DNA-dependent manner. Single-molecule DNA tethering experiments further revealed that AT-rich DNA sequences act as nucleation sites for the assembly and compaction of PfHP1-mediated heterochromatinization. We have also identified point mutations in the IDRs (intrinsically disordered regions) of PfHP1 that disrupt its phase separation as well as DNA compaction in vitro. An ectopic expression of PfHP1 phase separation and DNA compaction mutants led to dispersed nuclear localization, in contrast to the punctate appearance of the wild-type protein and altered chromatin binding at var genes. These results were corroborated with DiCre/loxP based conditional expression of the same PfHP1 mutants, which also led to the de-repression of multiple var genes (as many as 54 out of 60 var genes), mimicking the phenotype of PfHP1 depletion mutants. To assess the dynamic properties of PfHP1 condensates in vivo, we performed fluorescence recovery after photobleaching (FRAP) in live parasites, which revealed rapid fluorescence recovery, supporting their liquid-like behaviour. In conclusion, our study demonstrates the role of PfHP1 mediated LLPS in formation of heterochromatin and var gene silencing; unveiling a fundamental mechanism that drives antigenic variation in P. falciparum.
2026-02-16 | GSE299944 | GEO
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:Plasmodium falciparum var DBLa tag sequencing
| PRJNA386049 | ENA
Project description:Malaria caused by Plasmodium falciparum involves antigenic variation on the infected red blood cells through mutually exclusive expression of var genes. The repressed var genes have a distinct genome organization where they localize as a cluster near the nuclear periphery and are bound by PfHP1 (P. falciparum Heterochromatin Protein 1). However, the mode of regulation of var genes by PfHP1 remains unclear. In this study, we show that PfHP1 undergoes liquid-liquid phase separation (LLPS) in vitro in an RNA and DNA-dependent manner. Single-molecule DNA tethering experiments further revealed that AT-rich DNA sequences act as nucleation sites for the assembly and compaction of PfHP1-mediated heterochromatinization. We have also identified point mutations in the IDRs (intrinsically disordered regions) of PfHP1 that disrupt its phase separation as well as DNA compaction in vitro. An ectopic expression of PfHP1 phase separation and DNA compaction mutants led to dispersed nuclear localization, in contrast to the punctate appearance of the wild-type protein and altered chromatin binding at var genes. These results were corroborated with DiCre/loxP based conditional expression of the same PfHP1 mutants, which also led to the de-repression of multiple var genes (as many as 54 out of 60 var genes), mimicking the phenotype of PfHP1 depletion mutants. To assess the dynamic properties of PfHP1 condensates in vivo, we performed fluorescence recovery after photobleaching (FRAP) in live parasites, which revealed rapid fluorescence recovery, supporting their liquid-like behaviour. In conclusion, our study demonstrates the role of PfHP1 mediated LLPS in formation of heterochromatin and var gene silencing; unveiling a fundamental mechanism that drives antigenic variation in P. Falciparum.
2026-02-16 | GSE300206 | GEO
Project description:Malaria caused by Plasmodium falciparum involves antigenic variation on the infected red blood cells through mutually exclusive expression of var genes. The repressed var genes have a distinct genome organization where they localize as a cluster near the nuclear periphery and are bound by PfHP1 (P. falciparum Heterochromatin Protein 1). However, the mode of regulation of var genes by PfHP1 remains unclear. In this study, we show that PfHP1 undergoes liquid-liquid phase separation (LLPS) in vitro in an RNA and DNA-dependent manner. Single-molecule DNA tethering experiments further revealed that AT-rich DNA sequences act as nucleation sites for the assembly and compaction of PfHP1-mediated heterochromatinization. We have also identified point mutations in the IDRs (intrinsically disordered regions) of PfHP1 that disrupt its phase separation as well as DNA compaction in vitro. An ectopic expression of PfHP1 phase separation and DNA compaction mutants led to dispersed nuclear localization, in contrast to the punctate appearance of the wild-type protein and altered chromatin binding at var genes. These results were corroborated with DiCre/loxP based conditional expression of the same PfHP1 mutants, which also led to the de-repression of multiple var genes (as many as 54 out of 60 var genes), mimicking the phenotype of PfHP1 depletion mutants. To assess the dynamic properties of PfHP1 condensates in vivo, we performed fluorescence recovery after photobleaching (FRAP) in live parasites, which revealed rapid fluorescence recovery, supporting their liquid-like behaviour. In conclusion, our study demonstrates the role of PfHP1 mediated LLPS in formation of heterochromatin and var gene silencing; unveiling a fundamental mechanism that drives antigenic variation in P. Falciparum.
2026-02-16 | GSE300368 | GEO
Project description:Sequencing of P. falciparum var DBLa tags
| PRJNA1266761 | ENA