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A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5)

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE149774 | GEO | 2021/08/03

REPOSITORIES: GEO

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A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [WGS-Seq]

Project description:Gametocytogenesis, the process by which malaria parasites produce sexual forms that can infect mosquitoes, is essential for the transmission of malaria. A transcriptional switch of the pfap2-g gene triggers sexual commitment, but how the complex multi-step process is precisely programed remains largely unknown. Here, by systematic functional screening of a panel of ApiAP2 transcription factors, we identify six new apiAP2 members associated with gametocytogenesis in Plasmodium falciparum. Among these, PfAP2-G5 (PF3D7_1139300) was found to be indispensable for gametocytogenesis. This factor suppresses the transcriptional activity of the pfap2-g gene via binding to both the upstream region and exonic gene body, the latter is linked to the maintenance of local heterochromatin structure, thereby preventing initiation of sexual commitment. Removal of this repressive effect through pfap2-g5 knockout disrupts the asexual replication cycle and promotes sexual commitment accompanied by upregulation of pfap2-g expression. However, the gametocytes produced fail to mature fully. Further analyses show that PfAP2-G5 is essential for gametocyte maturation, and causes the down-regulation of pfap2-g and a set of early gametocyte genes activated by PfAP2-G prior to gametocyte development. Collectively, our findings reveal a regulation cascade of gametocyte production in malaria parasites, and provide a new target for transmission blocking interventions.

2021-08-03 | GSE175931 | GEO

A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [RNA-Seq]

2021-08-03 | GSE149772 | GEO

A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [ChIP-Seq HM]

2021-08-03 | GSE157709 | GEO

A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [ChIP-Seq TF]

2021-08-03 | GSE149773 | GEO

A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5)

Project description:A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5)

| PRJNA630081 | ENA

A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [WGS-Seq]

Project description:A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [WGS-Seq]

| PRJNA734316 | ENA

A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [RNA-Seq]

Project description:A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [RNA-Seq]

| PRJNA630083 | ENA

A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [ChIP-Seq HM]

Project description:A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [ChIP-Seq HM]

| PRJNA662514 | ENA

A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [ChIP-Seq TF]

Project description:A transcriptional repressor programs gametocytogenesis in human malaria parasites (PfAP2-G5) [ChIP-Seq TF]

| PRJNA630084 | ENA

Dissecting the role of PfAP2-G in malaria gametocytogenesis.

Project description:In the malaria parasite Plasmodium falciparum, the switch from asexual multiplication to sexual differentiation into gametocytes is essential for transmission to mosquitos. The transcription factor PfAP2-G is a key determinant of sexual commitment that orchestrates this crucial cell fate decision. Here we identify the direct targets of PfAP2-G and demonstrate that it dynamically binds hundreds of sites across the genome. We find that PfAP2-G is a transcriptional activator of early gametocyte genes, and identify differences in PfAP2-G occupancy between gametocytes derived via next-cycle and same-cycle conversion. Our data implicate PfAP2-G not only as a transcriptional activator of gametocyte genes, but also as a potential regulator of genes important for red blood cell invasion. We also find that regulation by PfAP2-G requires interaction with a second transcription factor, PfAP2-I. These results clarify the functional role of PfAP2-G during sexual commitment and early gametocytogenesis.

| S-EPMC7083873 | biostudies-literature

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