Plasmodium falciparum MORC protein modulates gene expression through interaction with heterochromatin
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ABSTRACT:
PROVIDER: PRJNA1007682 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25756857_1.fastq.gz | Fastqsanger.gz | |||
| SRR25756857_2.fastq.gz | Fastqsanger.gz | |||
| SRR25756858_1.fastq.gz | Fastqsanger.gz | |||
| SRR25756858_2.fastq.gz | Fastqsanger.gz | |||
| SRR25756859_1.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: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, MORC, 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, PF3D7_0420300, PF3D7_0613800, PF3D7_1107800 , 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.
2024-08-14 | PXD044256 | Pride
Project description:PfMORC modulates gene expression through interactions with heterochromatin in Plasmodium falciparum
| PRJNA999208 | ENA
Project description:Transposable elements (TEs) and DNA repeats are commonly targeted by DNA and histone methylation to achieve epigenetic gene silencing. We isolated mutations in two Arabidopsis genes, CRT1 and CRH6, which cause de-repression of DNA-methylated genes and TEs, but no losses of DNA or histone methylation. CRT1 and CRH6 are members of the conserved Microrchidia (MORC) ATPase family, predicted to catalyze alterations in chromosome superstructure. The crt1 and crh6 mutants show decondensation of pericentromeric heterochromatin, increased interaction of pericentromeric regions with the rest of the genome, and transcriptional defects that are largely restricted to loci residing in pericentromeric regions. Knockdown of the single MORC homolog in Caenorhabditis elegans also impairs transgene silencing. We propose that the MORC ATPases are conserved regulators of gene silencing in eukaryotes. For Col wild type control and each of two T-DNA mutants, a single sample each of small RNA (sRNA), mRNA-Seq, 5'-methylcytosine DNA methylation (BS-Seq), ChIP H3K9me2 histone methylation, and ChIP H3 histone control. For each of two EMS mutants, and as controls, their respective backgrounds, two batches of single mRNA samples, with the first batch also having a single mRNA sample for a double EMS mutant.
2012-05-02 | E-GEOD-37644 | biostudies-arrayexpress
Project description:Transposable elements (TEs) and DNA repeats are commonly targeted by DNA and histone methylation to achieve epigenetic gene silencing. We isolated mutations in two Arabidopsis genes, CRT1 and CRH6, which cause de-repression of DNA-methylated genes and TEs, but no losses of DNA or histone methylation. CRT1 and CRH6 are members of the conserved Microrchidia (MORC) ATPase family, predicted to catalyze alterations in chromosome superstructure. The crt1 and crh6 mutants show decondensation of pericentromeric heterochromatin, increased interaction of pericentromeric regions with the rest of the genome, and transcriptional defects that are largely restricted to loci residing in pericentromeric regions. Knockdown of the single MORC homolog in Caenorhabditis elegans also impairs transgene silencing. We propose that the MORC ATPases are conserved regulators of gene silencing in eukaryotes.
2012-05-03 | GSE37644 | GEO
Project description:Plasmodium falciparum heterochromatin formation
| PRJDB15278 | ENA
Project description:Heterochromatin is essential in all eukaryotic systems to maintain genome integrity, long-term gene repression and to help chromosome segregation during mitosis. However, heterochromatin regions must be restricted by boundary elements to avoid its spreading over actively transcribed loci. In Plasmodium falciparum, facultative heterochromatin is important to regulate parasite virulence, antigenic variation and transmission, but the underlying molecular mechanisms that regulate repressive regions remain unknown. To investigate this topic, we chose the ap2-g gene, that forms a strictly delimited heterochromatin island of 10 kb with no adjacent repressive chromatin. Using electrophoretic motility shift assay (EMSA) we identified an ap2-g exon element at the 3? end that shifts in the presence of nuclear extracts. Upon replacement of this region by a gfp gene, we observed a shift in the heterochromatin boundary, resulting in HP1 to spread over ~2 additional kb downstream. We used this DNA element to affinity purify candidate proteins followed by liquid-chromatography tandem mass-spectrometry (LC-MS/MS). The identified complexes are enriched in RNA-binding proteins, pointing to a potential role of RNA in the regulation of the ap2-g heterochromatin 3? boundary. Our results provide insight into the unexplored topic of heterochromatin boundary biology in P. falciparum and identifies a DNA element in the master regulator of sexual commitment that modulates heterochromatin spreading.
2020-02-18 | GSE145378 | GEO
Project description:Heterochromatin de novo formation and maintenance in Plasmodium falciparum
| PRJNA1213753 | ENA
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. one experimental sample
2010-05-06 | E-GEOD-17029 | biostudies-arrayexpress
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, MORC, during asexual blood stage development of the human malaria parasite Plasmodium falciparum. We show that PfMORC (PF3D7_1468100) interacts with a suite of nuclear proteins, including APETALA2 (ApiAP2) transcription factors (PfAP2-G5, PfAP2-O5, PfAP2-I, PF3D7_0420300, PF3D7_0613800, PF3D7_1107800, and PF3D7_1239200), a DNA helicase DS60 (PF3D7_1227100), and other chromatin remodelers (PfCHD1 and PfEELM2). 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 and chromatin organization.
| S-EPMC11483127 | biostudies-literature