PfMORC modulates gene expression through interactions with heterochromatin in Plasmodium falciparum
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ABSTRACT:
PROVIDER: PRJNA999208 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25437483.fastq.gz | Fastqsanger.gz | |||
| SRR25437484.fastq.gz | Fastqsanger.gz | |||
| SRR25437485.fastq.gz | Fastqsanger.gz | |||
| SRR25437486.fastq.gz | Fastqsanger.gz | |||
| SRR25437487.fastq.gz | Fastqsanger.gz |
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Project description:The MORC (microrchidia) family of proteins is highly conserved in all eukaryotic cells and have been shown to play diverse roles by forming protein-protein interactions with immune-responsive proteins, SWI chromatin remodeling complexes, histone deacetylases, and histone tail modifications across metazoans. To dissect the functional roles of MORC in the human malaria parasite, Plasmodium falciparum, we developed a glmS based ribozyme knockdown system to induce PfMORC knockdown upon glucosamine (GlcN) induction. We further conducted a transcriptomic analysis in PfMORC-HA-glmS knockdown parasites at the asexual stage to investigate alterations in global gene expression. Our results indicate an overrepresentation of downregulated genes belonging to the heterochromatin-associated hypervariable gene family proteins. Overall, we found that PfMORC controls the asexual gene expression of the P. falciparum and can be a potential target for malaria disease containment.
2023-11-15 | GSE241313 | GEO
Project description:Plasmodium falciparum MORC protein modulates gene expression through interaction with heterochromatin
| PRJNA1007682 | ENA
Project description:Plasmodium falciparum heterochromatin formation
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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:In the malaria parasite Plasmodium falciparum, changes in the distribution of heterochromatin at specific loci regulate the expression of clonally variant genes (CVGs), which play fundamental roles in host-parasite interactions. In addition to differences in heterochromatin between individual parasites associated with variant expression of CVGs, changes in heterochromatin distribution associated with different developmental stages have been described. However, while stage II/III gametocytes (sexual precursors) have an altered distribution of heterochromatin compared with asexual blood stages, it is unclear if heterochromatin changes already occur at the very early stages of sexual development. Here we used a transgenic parasite line in which sexual conversion can be conditionally induced to characterise the changes in heterochromatin distribution associated with the earliest stages of sexual development. We found that there were essentially no changes in sexual rings or stage I gametocytes compared with asexual blood stages, and remodelling of heterochromatin started at stage II or III of gametocyte development, with changes similar to those previously described in parasites of a different genetic background. Therefore, global redistribution of heterochromatin does not appear to play a role in the initial steps of sexual development. We also found that, for several genes, changes in expression associated with sexual development precede changes in the heterochromatin at their locus.
2024-10-09 | GSE252334 | GEO
Project description:In the malaria parasite Plasmodium falciparum, the expression of many genes is regulated by heterochromatin (HC) based on the histone mark tri-methylation of histone H3 lysine 9 (H3K9me3). HC assembly involves three distinct steps: de novo nucleation, spreading and maintenance. Nucleation, which consists in formation of HC in a previously euchromatic region, determines at which specific regions of the genome HC occurs, but this process is not well understood in malaria parasites. Here we investigated the DNA sequence cis determinants of HC nucleation in P. falciparum, using a screening approach based on integration of fragments from different heterochromatic genes into an euchromatic locus, followed by chromatin immunoprecipitation (ChIP). We found that fragments of var gene upstream regions nucleated HC efficiently, whereas fragments from the pfap2-g upstream region or from the mspdbl2 locus did not nucleate HC. Fragments from the beginning of the coding sequence (CDS) of pfap2-g nucleated HC with low efficiency, as evidenced by nucleation requiring long fragments of ~2 kb and occurring only in a fraction of the parasites. These results demonstrate that the primary DNA sequence is a main determinant of HC nucleation in P. falciparum. We also studied HC maintenance at the pfap2-g locus, which demonstrated that specific parts of the upstream region, different from the regions competent for HC nucleation, are required for maintenance. Together, our results provide initial insight into how HC is directed to specific loci and maintained in P. falciparum.
2025-04-07 | GSE287562 | 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
Project description:Heterochromatin de novo formation and maintenance in Plasmodium falciparum
| PRJNA1213753 | ENA
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