The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
A transcriptional switch underlies commitment to sexual development in malaria parasites
Open accessAbstract
The life cycles of many parasites involve transitions between disparate host species, requiring these parasites to go through multiple developmental stages adapted to each of these specialized niches. Transmission of malaria parasites (Plasmodium spp.) from humans to the mosquito vector requires differentiation from asexual stages replicating within red blood cells into non-dividing male and female gametocytes. Although gametocytes were first described in 1880, our understanding of the molecular mechanisms involved in commitment to gametocyte formation is extremely limited, and disrupting this critical developmental transition remains a long-standing goal. Here we show that expression levels of the DNA-binding protein PfAP2-G correlate strongly with levels of gametocyte formation. Using independent forward and reverse genetics approaches, we demonstrate that PfAP2-G function is essential for parasite sexual differentiation. By combining genome-wide PfAP2-G cognate motif occurrence with global transcriptional changes resulting from PfAP2-G ablation, we identify early gametocyte genes as probable targets of PfAP2-G and show that their regulation by PfAP2-G is critical for their wild-type level expression. In the asexual blood-stage parasites pfap2-g appears to be among a set of epigenetically silenced loci prone to spontaneous activation. Stochastic activation presents a simple mechanism for a low baseline of gametocyte production. Overall, these findings identify PfAP2-G as a master regulator of sexual-stage development in malaria parasites and mark the first discovery of a transcriptional switch controlling a differentiation decision in protozoan parasites.
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Genetic Analysis of the Human Malaria Parasite Plasmodium falciparum
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Self-citationA cascade of DNA-binding proteins for sexual commitment and development in Plasmodium
Sinha, A., Hughes, K. R., Modrzynska, K. K., Otto, T. D., Pfander, C., Dickens, N. J., Religa, A. A., Bushell, E., Graham, A. L., Cameron, R., et al. (2014) · Nature · doi:10.1038/nature12970 · Cited by 438
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New medicines to improve control and contribute to the eradication of malaria
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Improved synchronous production of Plasmodium falciparum gametocytes in vitro
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Cited by
A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium
Sinha, A., Hughes, K. R., Modrzynska, K. K., Otto, T. D., Pfander, C., Dickens, N. J., Religa, A. A., Bushell, E., Graham, A. L., Cameron, R., et al. (2014) · Nature · doi:10.1038/nature12970 · Cited by 438
Self-citationBrancucci, N. M. B., Gerdt, J. P., Wang, C., De Niz, M., Philip, N., Adapa, S. R., Zhang, M., Hitz, E., Niederwieser, I., Boltryk, S. D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.10.020 · Cited by 346
Heterochromatin Protein 1 Secures Survival and Transmission of Malaria Parasites
Brancucci, N. M. B., Bertschi, N. L., Zhu, L., Niederwieser, I., Chin, W. H., Wampfler, R., Freymond, C., Rottmann, M., Felger, I., Bozdech, Z., et al. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.07.004 · Cited by 299
Sexual development in Plasmodium parasites: knowing when it's time to commit
Josling, G. A., & Llinás, M. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3519 · Cited by 257
Self-citationBiology of Malaria Transmission
Meibalan, E., & Marti, M. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025452 · Cited by 251
Metadata
- Authors
- Kafsack, B. F. C., Rovira-Graells, N., Clark, T. G., Bancells, C., Crowley, V. M., Campino, S. G., Williams, A. E., Drought, L. G., Kwiatkowski, D. P., Baker, D. A., Cortés, A., & Llinás, M.
- Venue
- Nature
- Published
- 2014-02-23
- Volume
- 507
- Issue
- 7491
- Pages
- 248-252
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2021868082
- Cited by
- 537
- References
- 34
- FWCI
- 40.75
- Type
- journal article
- Language
- en
- Open access
- green
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- Kafsack, B. F. C., Rovira-Graells, N., Clark, T. G., Bancells, C., Crowley, V. M., Campino, S. G., Williams, A. E., Drought, L. G., Kwiatkowski, D. P., Baker, D. A., Cortés, A., & Llinás, M. (2014). A transcriptional switch underlies commitment to sexual development in malaria parasites. Nature. https://doi.org/10.1038/nature12920
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