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P.falciparum strain 3D7, SIR2 knockout

ABSTRACT: This experiment studies the effect of knocking out the transcriptional regulator SIR2 in 3D7 parasites. RNA was harvested from ring-stage parasites at 8 hours post-infection. Keywords = SIR2 Keywords = epigenetic regulation Keywords = antigenic variation Keywords = var Keywords = Plasmodium falciparum Keywords: other

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE2369 | GEO | 2005/03/08

SECONDARY ACCESSION(S): PRJNA91519

REPOSITORIES: GEO

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Comparative Genomic Hybridizaions of 3D7∆PfSir2a and NF54 compared to reference strain 3D7

Project description:Antigenic variation in Plasmodium falciparum is achieved by transcriptional switching amongst polymorphic var genes, enforced by epigenetic modification of chromatin. Histone-modifying ‘sirtuin’ enzymes PfSir2a and PfSir2b have been implicated in this process. We examined the effect of genetic disruption of sirtuins on var gene expression. Comparative Genomic Hybridization profile indicate that loss of PfSir2a in 3D7 resulted in strikingly rearranged chromosomes.

2014-10-02 | GSE61940 | GEO

3D7 PfHda2 Knockdown vs. Wildtype

Project description:The asexual forms of the malaria parasite Plasmodium falciparum are uniquely adapted for chronic persistence in human red blood cells, continuously evading the immune system using an epigenetically regulated process. However, parasite survival on a population level also requires transmission of sexual parasite forms to subsequent human hosts. Here, we reveal that the essential nuclear gene, P. falciparum histone deacetylase 2 (PfHda2), silences specific subsets of genes involved in antigenic variation or conversion to sexual stages. Two parallel timecourses resulting in a total of 22 samples (11 wildtype, 11 PfHda2 knockdown) were hybridized against a Cy3-labeled reference pool of 3D7 mixed stage parasites on a two-color array.

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2021-05-17 | GSE149393 | GEO

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Project description:To investigate the role of cell-cycle-dependent Sir2 recruitment, we collected Sir2-ChIP samples after HU treatment.

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Rap1, Sir2, Sir3, Sir4 immunoprecipitations

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Screening of differentially expressed genes in three Plasmodium falciparum parasite lines [RNA-seq]

Project description:We performed RNA-Seq analysis with synchronized 0-6h ring stage parasites of three P.falciparum lines within their third life cycle, to study the change of expression profiling when knocking down PfSWIB. The comparison analysis on screening of differentially expressed genes was done in parasite lines including 3D7(wild type: blank control), PfSWIB (wild type: self-control) and PfSWIB∆ (PfSWIB knockdown). Approximately 10.8% of the transcripts showed up-regulation between the PfSWIB-KD and two WT parasite, whereas 11.9% showed down-regulation (Fold change>1.5, P<0.05). Hierarchical clustering of differentially expressed genes uncovered several transcription factors such as PfApiAP2 family and PfSir2B, as well as certain histone modification enzymes, which proved to be involved in regulating on var gene transcription. We further screened out a number of var genes which exhibited differential expression among different lines, and performed qPCR on 44 diﬀerentially expressed vars in the PfSWIB vs PfSWIB∆ comparison group based on the RNA-seq results, to study the transcription patterns of upsA-, upsB- and upsC-subtype var genes. We found that most upsA- and upsC- type vars were significant down-regulated in PfSWIB∆ line. In contrast, the expression pattern of partial upsB vars presented a distinct change in PfSWIB∆ line. The RNA-seq and qPCR analysis provide a better understanding of the mechanism and function of PfSWIB on regulating the expression switching and clonal variation of var gene family contributing to the pathogenesis in malaria parasites.

2020-02-18 | GSE141155 | GEO

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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

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2012-07-14 | E-GEOD-33868 | biostudies-arrayexpress

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