Sex-specific gene regulation in malaria parasites by an AP2 Family Transcription Factor [ChIP-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Plasmodium berghei ANKA
PROVIDER: GSE114094 | GEO | 2019/05/05
REPOSITORIES: GEO
Similar Datasets
Project description:Malaria gametocytes, the precursors of gametes, is the stage essential for malaria transmission to the mosquito vector. In the circulation they arise from asexual erythrocytic stages and then develop into mature females and males. Identification of sex-specific transcription factors is a key to understand biology of this stage. However, despite of intensive studies, none of them have been identified yet. In this paper we report an AP2 family transcription factor AP2-FG is responsible for female-specific gene expression.
2019-05-05 | GSE114095 | GEO
Project description:AP2-FG is a female-specific transcription factor (TF) that plays an essential role in female gametocyte development. AP2-FG activates hundreds of genes by binding to a female-specific ten-base cis-acting element. Here, we report that in the rodent malaria parasite Plasmodium berghei, another female-specific TF designated as a partner of AP2-FG (PFG), controls gene expression in female gametocytes cooperatively with AP2-FG. Transcriptional mechanisms were analyzed in Plasmodium berghei female gametocytes.
2024-01-22 | GSE226020 | GEO
Project description:AP2-FG is a female-specific transcription factor (TF) that plays an essential role in female gametocyte development. AP2-FG activates hundreds of genes by binding to a female-specific ten-base cis-acting element. Here, we report that in the rodent malaria parasite Plasmodium berghei, another female-specific TF designated as a partner of AP2-FG (PFG), controls gene expression in female gametocytes cooperatively with AP2-FG. Transcriptional mechanisms were analyzed in Plasmodium berghei female gametocytes.
2024-01-22 | GSE226021 | GEO
Project description:AP2-FG is a female-specific transcription factor (TF) that plays an essential role in female gametocyte development. AP2-FG activates hundreds of genes by binding to a female-specific ten-base cis-acting element. Here, we report that in the rodent malaria parasite Plasmodium berghei, another female-specific TF designated as a partner of AP2-FG (PFG), controls gene expression in female gametocytes cooperatively with AP2-FG.
2024-01-22 | GSE226027 | GEO
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
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
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. At the same time we have generated purified transcriptomes of male and female gametocytes for the reference
2021-03-13 | GSE168817 | GEO
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
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 | GSE66189 | GEO
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