Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Global Transcriptional Repression: Initial and Essential Step for Plasmodium Sexual Development [ChIP-seq]

ABSTRACT: Gametocytes are nonreplicative sexual forms that mediate malaria transmission to a mosquito vector. They are generated from asexual blood stage parasites, which proliferate in the circulation. However, it remains largely unknown as to how this transition is genetically regulated. Here, we report that an Apetala2 (AP2) family transcription factor, AP2-G2, regulates the transition as a transcriptional repressor. Disruption of AP2-G2 in the rodent malaria parasites, Plasmodium berghei, did not prevent commitment to the sexual stage but halted their development before manifesting sex-specific morphologies. ChIP-seq analysis revealed that AP2-G2 targets approximately 1,500 genes and recognizes a five-base motif on their promoters. Most of these target genes are required for asexual proliferation in the blood by the parasites, thereby suggesting that AP2-G2 blocks the program for asexual replication of parasites in the blood. DNA microarray analysis showed that the identified targets constituted approximately 70% of the upregulated genes in AP2-G2-depleted parasites, and a promoter assay using a centromere plasmid demonstrated that the binding motif functions as a cis-acting negative regulatory element. These results suggest that global transcriptional repression, which occurs during the initial phase of gametocytogenesis, is an essential step to promote conversion to the sexual stage.

ORGANISM(S): Plasmodium berghei ANKA

PROVIDER: GSE66189 | GEO | 2015/10/01

SECONDARY ACCESSION(S): PRJNA276082

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Global Transcriptional Repression: Initial and Essential Step for Plasmodium Sexual Development [expression array]

Project description:Gametocytes are nonreplicative sexual forms that mediate malaria transmission to a mosquito vector. They are generated from asexual blood stage parasites, which proliferate in the circulation. However, it remains largely unknown as to how this transition is genetically regulated. Here, we report that an Apetala2 (AP2) family transcription factor, AP2-G2, regulates the transition as a transcriptional repressor. Disruption of AP2-G2 in the rodent malaria parasites, Plasmodium berghei, did not prevent commitment to the sexual stage but halted their development before manifesting sex-specific morphologies. ChIP-seq analysis revealed that AP2-G2 targets approximately 1,500 genes and recognizes a five-base motif on their promoters. Most of these target genes are required for asexual proliferation in the blood by the parasites, thereby suggesting that AP2-G2 blocks the program for asexual replication of parasites in the blood. DNA microarray analysis showed that the identified targets constituted approximately 70% of the upregulated genes in AP2-G2-depleted parasites, and a promoter assay using a centromere plasmid demonstrated that the binding motif functions as a cis-acting negative regulatory element. These results suggest that global transcriptional repression, which occurs during the initial phase of gametocytogenesis, is an essential step to promote conversion to the sexual stage.

2015-10-01 | GSE66188 | GEO

ChIP-seq on PfAP2-G2 in trophozoite and gametocyte stages of parasites.

Project description:Differentiation from asexual blood stages to sexual gametocytes is required for transmission of malaria parasites from the human host to mosquitos, where sexual fertilization occurs to complete the lifecycle. Although preventing gametocyte development would block parasite transmission, the molecular mechanisms underlying sexual commitment and gametocyte maturation are still relatively unknown. Previous studies identified an ApiAP2 protein, AP2-G2, which plays a critical role in gametocyte maturation in rodent malaria parasite Plasmodium berghei by acting as the repressor of asexual stage genes in gametocytes. In this work we characterize the P. falciparum orthologue (PF3D7_1408200) of PbAP2-G2 and report that it plays a critical role in maturation of gametocytes. Disruption of pfap2-g2 did not obstruct commitment to sexual development but the majority of parasites were unable to develop normally beyond stage III gametocytes. In asexual stages PfAP2-G2 binds to the promoters of wide variety of genes expressed in diverse range of parasite’s life cycle stages including gametocytes, mosquito lifecycle stages early ring stage genes and genes encoding for proteins involved in egress and invasion. Surprisingly, we also identify binding of PfAP2-G2 in the gene body of almost 3000 genes. We could also show that PfAP2-G2 interacts with chromatin remodeling proteins and another ApiAP2 protein (PF3D7_1139300) whose motif is also overrepresented in the ChIP-seq data. Overall this work suggests that PfAP2-G2 is a transcriptional regulator that regulates genes possibly by recruiting additional transcription factors and chromatin remodeling machinery and plays a critical role in the development of malaria parasites as they transition from the asexual stage to gametocytes.

2021-02-16 | GSE157753 | GEO

A knockout screen of ApiAP2 genes reveals networks of interacting transcriptional regulators controlling the Plasmodium life cycle.

Project description:The family of apicomplexa-specific proteins with DNA binding AP2 domains (ApiAP2s) includes sequence-specific transcription factors that are key regulators of development in malaria parasites. However, functions for the majority of ApiAP2 genes remain unknown. Here, a systematic knockout screen in Plasmodium berghei identifies ten ApiAP2 genes essential for mosquito transmission, of which four are critical for the formation of infectious ookinetes and three for sporogony. We describe unexpected non-essential functions for AP2-O and AP2-SP proteins in blood stages and identify AP2-G2 as a universal repressor active in both, asexual and sexual stages. Comparative transcriptomics across mutants and developmental stages reveals clusters of co-regulated genes with shared cis elements in their promoters, whose expression can be controlled positively or negatively by different ApiAP2 gene deletions. We propose that stage-specific interactions between ApiAP2 proteins on partly overlapping sets of target genes generate the complex transcriptional network that controls the Plasmodium life cycle.

2017-02-08 | PXD005180 | Pride

Differential gene expression in ap2-g and ap2-g2 mutants of Plasmodium berghei

Project description:Commitment to and completion of sexual development are essential for malaria parasites to be transmitted through mosquitoes. The molecular mechanism(s) responsible for these processes however, remain largely unknown. We have identified two transcription factors (both belonging to the AP2 family) essential for gametocytogenesis. AP2-G mutants are characterised by a complete inability to produce gametocytes. In AP2-G2 mutants the gametocytaemia is very significantly reduced but not completely abolished. We have performed the microarray experiments in order to cokmpare the transcriptomes of these mutantnts to the WT parasites and between each other. As P.berghei parasites are characterised by asynchronous development in the rodent host, the different stage composition of the sample would impact the analysis. Therefore parasites were harvested and matured in in vitro to the schizont stage

2013-12-03 | GSE52859 | GEO

Differential gene expression in ap2-g and ap2-g2 mutants of Plasmodium berghei

2013-12-03 | E-GEOD-52859 | biostudies-arrayexpress

Plasmodium falciparum PfAP2-G2 KO gametocyte microarray timecourse

Project description:Differentiation from asexual blood stages to sexual gametocytes is required for transmission of malaria parasites from the human to the mosquito host. Preventing gametocyte commitment and development would block parasite transmission, but the underlying molecular mechanisms behind these processes remain poorly understood. Here, we report that the ApiAP2 transcription factor, PfAP2-G2 (PF3D7_1408200) plays a critical role in the maturation of Plasmodium falciparum gametocytes. PfAP2-G2 binds to the promoters of a wide array of genes that are expressed at many stages of the parasite life cycle. Interestingly, we also find binding of PfAP2-G2 within the gene body of almost 3000 genes, which strongly correlates with the location of H3K36me3 and several other histone modifications as well as Heterochromatin Protein 1 (HP1), suggesting that occupancy of PfAP2-G2 in gene bodies may serve as an alternative regulatory mechanism. Disruption of pfap2-g2 does not impact asexual development, parasite multiplication rate, or commitment to sexual development but the majority of sexual parasites are unable to mature beyond stage III gametocytes. The absence of pfap2-g2 leads to overexpression of 28% of the genes bound by PfAP2-G2 and none of the PfAP2-g2 bound are downregulated, suggesting that it is a repressor. We also find that PfAP2-G2 interacts with chromatin remodeling proteins, a microrchidia (MORC) protein, and another ApiAP2 protein (PF3D7_1139300). Overall our data demonstrate that PfAP2-G2 is an important transcription factor that establishes an essential gametocyte maturation program in association with other chromatin-related proteins.

2021-02-01 | GSE160924 | GEO

Plasmodium falciparum PfAP2-G2 KO asexual microarray timecourse

2021-02-01 | GSE160923 | GEO

Transcriptome changes during inducible gametocytogenesis in Plasmodium berghei parasites

Project description:During the malaria infection, Plasmodium parasites invade the host’s red blood cells where they can differentiate into two different life forms. The majority will replicate asexually and infect new erythrocytes. A small percentage, however, will transform into gametocytes – a specialized sexual stage able to survive and develop when taken up by Anopheles mosquito. As the gametocytes ensure the parasite’s transmission to a new host, their generation is an attractive target for new antimalarial interventions. The molecular mechanisms controlling gametocytogenesis, however, remain largely unknown due to the technical challenges: the early gametocytes are morphologically indistinguishable from asexual parasites and present in very low numbers during the infection. Recently, AP2-G - a transcription factor from an apicomplexa-specific apiAP2 family – was described as indispensable for gametocyte commitment in both human malaria parasite Plasmodium falciparum and rodent malaria model Plasmodium berghei. Therefore, we have decided to test whether the overexpression of this factor alone could increase gametocyte production and enable the investigation of uncharacterised, earliest stages of gametocyte development. To this end, we have engineered PBGAMi - a Plasmodium berghei line, in which all parasites were ap2-g deficient by default but able to overexpress it when induced with rapamycin. While the control parasites (PBGAMi R-), as expected, differentiated into asexual forms (schizonts) only, almost all rapamycin-treated parasites (PBGAMi R+) transformed into gametocytes. We used the generated line to perform RNA-seq analysis of the R- and R+ populations at different time points of their development and identify the changes arising between them, mapping the sequence of events leading to the formation of gametocytes.

2018-06-30 | GSE110201 | GEO

Transcriptome changes during inducable gametocytogenesis in Plasmodium berghei parasites

2021-03-13 | GSE168817 | GEO

GDV1 triggers sexual conversion and differentiation in malaria parasites by antagonizing HP1-dependent gene silencing

Project description:Malaria is caused by Plasmodium parasites that proliferate through iterative cycles of intra-erythrocytic replication. During each cycle a small number of parasites differentiate into gametocytes, the only forms able to infect the mosquito vector and transmit malaria. Sexual commitment is triggered by activation of AP2-G, the master transcriptional regulator of gametocytogenesis. Heterochromatin protein 1 (HP1)-dependent silencing of ap2-g prevents sexual conversion and secures proliferation. Here, we identify gametocyte development 1 (GDV1) as the first upstream activator of the sexual differentiation pathway in P. falciparum. Induction of GDV1 expression is sufficient to activate AP2-G expression and sexual differentiation. We found that GDV1 targets heterochromatin and triggers HP1 eviction preferentially at ap2-g and other gametocyte-specific genes. We further demonstrate that GDV1-dependent activation of ap2-g is controlled via a gdv1 antisense RNA. In summary, we identify GDV1 as an unprecedented cell fate decision factor that induces sexual differentiation by antagonizing HP1-dependent gene silencing.

2018-05-04 | GSE94901 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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