Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetic regulation of Plasmodium falciparum adaptive plasticity in the mosquito

ABSTRACT: 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.

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE68667 | GEO | 2017/01/18

SECONDARY ACCESSION(S): PRJNA283324

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Regulation of Puf2 Expression is Critical for Plasmodium Sporozoite Development and Maintenance of Sporozoite Transmissibility

Project description:MalariaM-bM-^@M-^Ys cycle of infection requires parasite transmission between a mosquito vector and a vertebrate host. Plasmodium regulates transmission by translationally repressing specific mRNAs until their products are needed. We demonstrate that the Plasmodium yoelii Pumilio-FBF family member Puf2 allows the sporozoite to retain its infectivity in the mosquito salivary glands while awaiting transmission. Puf2 mediates this critical feature solely through its RNA-Binding Domain (RBD) likely by protecting and silencing specific mRNAs. Puf2 storage granules are distinct from stress granules and P-bodies and dissolve rapidly after infection of hepatocytes, likely releasing the protected and silenced transcripts for M-bM-^@M-^Xjust-in-timeM-bM-^@M-^Y translation by early exoerythrocytic forms (EEFs). Further corroborating this model, pypuf2- sporozoites have no apparent defect in host infection early after invading the salivary glands, but become progressively noninfectious and subsequently prematurely transform into EEFs during prolonged salivary gland residence. In contrast, the premature overexpression of Puf2 in oocysts causes striking deregulation of sporozoite maturation, resulting in fewer oocyst sporozoites that are non-infectious and unable to colonize the salivary glands. Maintenance of Puf2 expression in liver stage parasites produces no phenotype, suggesting that a window of permissive expression exists. Finally, by conducting the first comparative RNAseq analysis of Plasmodium sporozoites, we have uncovered that Puf2 may play a role in both the protection of specific transcripts as well as RNA turnover via the CCR4/Not complex. These findings uncover requirements for maintaining a window of opportunity for the malaria parasite to accommodate the unpredictable moment of transmission from mosquito to vertebrate host. Wild-type (Py17XNL) and pypuf2 -salivary gland sporozoites

2012-10-27 | E-GEOD-41873 | biostudies-arrayexpress

The Plasmodium falciparum histone methyltransferase PfSET10 is dispensable for the regulation of antigenic variation and gene expression in blood stage parasites

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

Regulation of Puf2 Expression is Critical for Plasmodium Sporozoite Development and Maintenance of Sporozoite Transmissibility

Project description:Malaria’s cycle of infection requires parasite transmission between a mosquito vector and a vertebrate host. Plasmodium regulates transmission by translationally repressing specific mRNAs until their products are needed. We demonstrate that the Plasmodium yoelii Pumilio-FBF family member Puf2 allows the sporozoite to retain its infectivity in the mosquito salivary glands while awaiting transmission. Puf2 mediates this critical feature solely through its RNA-Binding Domain (RBD) likely by protecting and silencing specific mRNAs. Puf2 storage granules are distinct from stress granules and P-bodies and dissolve rapidly after infection of hepatocytes, likely releasing the protected and silenced transcripts for ‘just-in-time’ translation by early exoerythrocytic forms (EEFs). Further corroborating this model, pypuf2- sporozoites have no apparent defect in host infection early after invading the salivary glands, but become progressively noninfectious and subsequently prematurely transform into EEFs during prolonged salivary gland residence. In contrast, the premature overexpression of Puf2 in oocysts causes striking deregulation of sporozoite maturation, resulting in fewer oocyst sporozoites that are non-infectious and unable to colonize the salivary glands. Maintenance of Puf2 expression in liver stage parasites produces no phenotype, suggesting that a window of permissive expression exists. Finally, by conducting the first comparative RNAseq analysis of Plasmodium sporozoites, we have uncovered that Puf2 may play a role in both the protection of specific transcripts as well as RNA turnover via the CCR4/Not complex. These findings uncover requirements for maintaining a window of opportunity for the malaria parasite to accommodate the unpredictable moment of transmission from mosquito to vertebrate host.

2012-10-27 | GSE41873 | GEO

Transcription profiling by array of Plasmodium berghei wild type and puf2 knock out in a time series

Project description:Many eukaryotic developmental and cell fate decisions are effected post-transcriptionally that mechanistically involve RNA binding proteins as regulators of translation of key mRNAs. In the unicellular eukaryote malaria parasite, Plasmodium, one of the most dramatic changes in cell morphology and function occurs during transmission between mosquito and human host. In the mosquito salivary glands, Plasmodium sporozoites are slender, motile and remain infectious for several weeks; only after transmission and liver cell invasion, does the parasite rapidly transform into a round, non-motile exo-erythrocytic form (EEF) that gives rise to thousands of infectious merozoites to be released into the blood stream. Here we demonstrate a Plasmodium homolog of the RNA binding protein, Pumilio, as a key regulator of the sporozoite to EEF transformation. In the absence of Pumilio-2 (Puf2) Plasmodium berghei sporozoites initiate early stage EEF development inside mosquito salivary glands with characteristic morphological changes; puf2- salivary gland sporozoites lose gliding motility, cell traversal ability and are less infective. Global expression profiling confirmed that transgenic parasites exhibit genome-wide transcriptional adaptations typical for Plasmodium intra-hepatic development. The data demonstrate that Puf2 is a key player in regulating developmental control, and imply that transformation of salivary gland-resident sporozoites into early liver stage parasites is regulated by a post-translational mechanism.

2010-11-01 | E-TABM-1067 | biostudies-arrayexpress

Comparative Total RNA-seq between WT and alba4-null Plasmodium yoelii parasites

Project description:To determine the role of ALBA4 in mRNA homeostasis in Plasmodium parasites, we performed comparative total RNA-seq between a WT-GFP line and an alba4-null line. We performed these experiments at three points in the life cycle - asexual (schizont), sexual (gametocyte), and oocyst sporozoite stages. We found that ALBA4 has a multi-faceted role in mRNA homeostasis, and is involved in mRNA fate determination. ALBA4 appears to act in a stage-specific manner, affecting different sets of transcripts in each stage. Our data suggests that ALBA4 plays opposing roles - possibly promoting degradation in schizonts, while promoting mRNA protection in gametocytes. In oocyst sporozoites, it appears that ALBA4 has a mixed role, and may be involved in both degradation and protection of mRNAs.

2017-08-25 | GSE81834 | GEO

Proteomic view of the Plasmodium falciparum life cycle

Project description:The completion of the Plasmodium falciparum clone 3D7 genome provides a basis on which to conduct comparative proteomics studies of this human pathogen. Here, we applied a high-throughput proteomics approach to identify new potential drug and vaccine targets and to better understand the biology of this complex protozoan parasite. We characterized four stages of the parasite life cycle (sporozoites, merozoites, trophozoites and gametocytes) by multidimensional protein identification technology. Functional profiling of over 2,400 proteins agreed with the physiology of each stage. Unexpectedly, the antigenically variant proteins of var and rif genes, defined as molecules on the surface of infected erythrocytes, were also largely expressed in sporozoites. The detection of chromosomal clusters encoding co-expressed proteins suggested a potential mechanism for controlling gene expression. Keywords: ordered

2002-12-22 | E-GEOD-92 | biostudies-arrayexpress

Proteomic view of the Plasmodium falciparum life cycle

2002-12-23 | GSE92 | GEO

Transcriptional profiling defines histone acetylation as a regulator of gene expression during human-to-mosquito transmission of the malaria parasite Plasmodium falciparum

Project description:Transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by the intraerythrocytic gametocytes, which, once taken up during a blood meal, become activated to initiate sexual reproduction. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they are crucial for spreading the tropical disease. During gametocyte maturation, different repertoires of genes are switched on and off in a well-coordinated sequence, pointing to regulatory mechanisms of gene expression. While epigenetic gene control has been studied during erythrocytic schizogony of P. falciparum, little is known about this process during parasite human-to-mosquito transmission of the parasite. To unveil the potential role of histone acetylation during gene expression in gametocytes, we carried out a microarray-based transcriptome analysis on gametocytes treated with the histone deacetylase inhibitor trichostatin A (TSA).

2017-05-24 | GSE99223 | GEO

Pleiotropic Roles for the Plasmodium berghei RNA Binding Protein UIS12 in Anopheles Transmission and Sporogony

Project description:Colonization of the mosquito host by Plasmodium parasites is achieved by sexually differentiated gametocytes. Gametocytogenesis, gamete formation and fertilization are tightly regulated processes, and translational repression is a major regulatory mechanism for stage conversion. Here, we present a characterization of a Plasmodium berghei RNA binding protein, UIS12, that contains two conserved eukaryotic RNA recognition motifs (RRM). Targeted gene deletion results in viable parasites that replicate normally during blood infection, but form fewer gametocytes. Upon transmission to Anopheles stephensi mosquitoes, both numbers and size of midgut-associated oocysts are impaired. As a consequence, no salivary gland sporozoites are formed indicative of a complete life cycle arrest in the mosquito vector. Comparative transcript profiling in mutant and wild-type infected red blood cells revealed downregulation of mRNAs coding for signature gamete-, ookinete- and oocyst-specific proteins in uis12(-) parasites. Together, our findings indicate multiple roles for UIS12 in regulation of gene expression after blood infection in good agreement with the pleiotropic defects that terminate successful sporogony and onward transmission to a new vertebrate host.

2021-03-05 | GSE152686 | GEO

A system for functional studies of the major virulence factor of malaria parasites

Project description:The major virulence factor of Plasmodium falciparum parasites, PfEMP1 is expressed by a multigene family, termed var genes. Here selection linked integration (SLI) was utilized to modify var genes in P. falciparum parasites to select for parasite populations expressing a single var gene. Bulk RNA was isolated from ring stage parasites of these SLI parasite populations and analyzed with next generation sequencing. The proportion of exon 2 transcripts of var genes normalized to transcripts per million was determined per cell line to confirm the predominant expression of the desired var gene.

2024-06-14 | GSE267413 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data