The PfAP2-G2 transcription factor is a critical regulator of gametocyte maturation
| Autor: | Riëtte van Biljon, Lindsey M. Orchard, Suprita Singh, Manuel Llinás, Heather J. Painter, Shaun Mahony, Naomi Yamada, Joana M. Santos |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Plasmodium falciparum
Protozoan Proteins Repressor Biology Microbiology Chromatin remodeling Article Gametogenesis 03 medical and health sciences Gametocyte Humans Malaria Falciparum Molecular Biology Transcription factor Gene 030304 developmental biology 0303 health sciences Life Cycle Stages 030306 microbiology Gene Expression Regulation Developmental Promoter biology.organism_classification Cell biology Histone Germ Cells biology.protein Heterochromatin protein 1 Transcription Factors |
| Zdroj: | Mol Microbiol |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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