ApiAP2 regulation of clonally variant genes in Plasmodium falciparum
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB20833 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The survival of malaria parasites in the changing human blood environment largely depends on their ability to alter gene expression by epigenetic mechanisms. The active state of Plasmodium falciparum clonally variant genes is associated with euchromatin characterized by the histone mark H3K9ac, whereas the silenced state is characterized by H3K9me3-based heterochromatin. However, the localization of the euchromatin-heterochromatin transitions associated with expression switches in different clonally variant genes has not been characterized. Here we compared the distribution of heterochromatin between subclones of the same genetic background with different patterns of expressed and silenced clonally variant genes to identify at a genome-wide level the patterns associated with the different transcriptional states. We found that de novo heterochromatin formation or complete disruption of a heterochromatin domain are relatively rare events, and in the majority of loci expression switches can be explained by expansion or retraction of heterochromatin. We describe different modalities of heterochromatin changes linked to transcriptional differences, revealing a complex scenario. Despite this complexity, heterochromatin distribution patterns generally enable prediction of the transcriptional state of clonally variant genes. Some subclones expressed and had in an active chromatin state several var genes simultaneously. We also found that heterochromatin levels in the putative regulatory region of the gdv1-as non-coding RNA, previously involved in sexual commitment, varied between parasite lines with different sexual conversion rates.
2022-11-03 | GSE208560 | GEO
Project description:The survival of malaria parasites in the changing human blood environment largely depends on their ability to alter gene expression by epigenetic mechanisms. The active state of Plasmodium falciparum clonally variant genes is associated with euchromatin characterized by the histone mark H3K9ac, whereas the silenced state is characterized by H3K9me3-based heterochromatin. However, the localization of the euchromatin-heterochromatin transitions associated with expression switches in different clonally variant genes has not been characterized. Here we compared the distribution of heterochromatin between subclones of the same genetic background with different patterns of expressed and silenced clonally variant genes to identify at a genome-wide level the patterns associated with the different transcriptional states. We found that de novo heterochromatin formation or complete disruption of a heterochromatin domain are relatively rare events, and in the majority of loci expression switches can be explained by expansion or retraction of heterochromatin. We describe different modalities of heterochromatin changes linked to transcriptional differences, revealing a complex scenario. Despite this complexity, heterochromatin distribution patterns generally enable prediction of the transcriptional state of clonally variant genes. Some subclones expressed and had in an active chromatin state several var genes simultaneously. We also found that heterochromatin levels in the putative regulatory region of the gdv1-as non-coding RNA, previously involved in sexual commitment, varied between parasite lines with different sexual conversion rates. Gene expression data for subclones A7, E5 and B11 (3D7-B stock).
2022-11-03 | GSE208131 | GEO
Project description:The malaria parasite Plasmodium falciparum relies on clonally variant gene expression in order to escape immune recognition and secure continuous proliferation during blood stage infection. Here, we studied the role of heterochromatin protein 1 (HP1), an evolutionary conserved regulator of heritable gene silencing, in the biology of P. falciparum blood stage parasites. We demonstrate that conditional PfHP1 depletion de-represses hundreds of heterochromatic virulence genes and disrupts the elusive mechanism underlying mutually exclusive expression and antigenic variation of PfEMP1. Intriguingly, we also discovered that the PfHP1-dependent regulation of an ApiAP2 transcription factor controls the switch from asexual parasite proliferation to sexual differentiation. This uncovers the first mechanistic insight into the unknown pathway triggering gametocyte conversion and establishes a new concept of HP1-dependent cell fate decision in unicellular eukaryotes. P. falciparum 3D7 parasites expressing endogenous PfHP1-GFP-DD were grown in presence of 4nM WR/625nM Shield-1 (3D7/HP1ON) or 4nM WR (3D7/HP1OFF). RNA extracted from these samples at eleven consecutive time points each was processed for microarray analysis.
2014-07-09 | E-GEOD-53176 | biostudies-arrayexpress
Project description:During the progress through its complex life cycle, the malaria parasite requires strict control of gene expression but the mechanism controlling this process remain poorly understood and unexplored for therapeutic purposes. A group of the apicomplexa-specific putative transcription factors with AP2 DNA binding domain (apiAP2) has been identified as the major regulators of the parasite transcriptome at multiple stages. The targets and the role of the majority of the members of the family however are unknown.
2017-03-08 | GSE80634 | GEO
Project description:Replication origin mapping in the malaria parasite Plasmodium falciparum
2022-08-04 | GSE210010 | GEO
Project description:The Apicomplexa constitute a large phylum of parasitic protozoans with complex life cycles that typically include meiotic sex. The life cycle of the malaria parasite, Plasmodium falciparum, includes obligate transition and stage development between a human and mosquito host. Asexual parasite replication in the human erythrocytes is followed by differentiation which leads to the formation of a precursor gamete stage, referred to as gametocytes. The gametocyte stage is solely responsible for malaria transmission into the mosquito vector where gamete fusion followed by meiosis occurs. How the parasite differentiates into male and female gametocytes in the absence of sex chromosomes largely remains an open question. Here, we combine FACS-based cell enrichment of a gametocyte reporter line followed by single-cell RNA-seq, to enable targeted characterization of the entire gametocyte developmental stage. Our data defines differential transcription programs during male and female gametocyte development and highlights a bifurcation point for sexual cell fate. We perform prediction analyses of novel candidate driver genes underlying P. falciparum sexual cell fate. Additionally, we delineate the timing of expression of members of the ApiAP2 family of transcription factors and predict their specificity in male or female P. falciparum gametocyte development.
2024-05-31 | GSE226145 | GEO
Project description:The malaria parasite Plasmodium falciparum relies on clonally variant gene expression in order to escape immune recognition and secure continuous proliferation during blood stage infection. Here, we studied the role of heterochromatin protein 1 (HP1), an evolutionary conserved regulator of heritable gene silencing, in the biology of P. falciparum blood stage parasites. We demonstrate that conditional PfHP1 depletion de-represses hundreds of heterochromatic virulence genes and disrupts the elusive mechanism underlying mutually exclusive expression and antigenic variation of PfEMP1. Intriguingly, we also discovered that the PfHP1-dependent regulation of an ApiAP2 transcription factor controls the switch from asexual parasite proliferation to sexual differentiation. This uncovers the first mechanistic insight into the unknown pathway triggering gametocyte conversion and establishes a new concept of HP1-dependent cell fate decision in unicellular eukaryotes.
2014-07-09 | GSE53176 | GEO
Project description:This experiment characterizes the transcriptome of the human malaria parasite, P. falciparum at 8 different stages of the intraerythrocytic cycle
2010-10-28 | GSE23865 | GEO
Project description:This experiment characterizes the transcriptome of the human malaria parasite, P. falciparum at 8 different stages of the intraerythrocytic cycle Examination of polyA selected RNA in Plasmodium falciparum 3D7 strain at 8 different stages using RNA-seq
2010-10-28 | E-GEOD-23865 | biostudies-arrayexpress
Project description:Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum parasites to the fluctuating conditions of the human host, but their expression patterns under the natural conditions of the blood circulation have been characterized in detail only for a few specific gene families. Here we provide a detailed characterization of the full P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in non-immune human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occur for CVGs. Specifically, we observed a major increase in the transcript levels of most members of the pfmc-2tm and gbp families and of specific genes of other families, in addition to previously reported changes in var and clag3 genes. The expression patterns were almost identical between parasites obtained from the different volunteers. Large transcriptional differences correlate with changes in the distribution of histone modifications associated with heterochromatin, confirming their epigenetic nature. The analysis of parasites collected at different points along the infection indicates that when parasites pass through transmission stages, the epigenetic memory at CVG loci is lost, resulting in a reset of their expression state and reestablishment of new epigenetic patterns.
2021-07-01 | GSE166258 | GEO