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Science. 2018 Mar 16;359(6381):1259-1263. doi: 10.1126/science.aan6042.

GDV1 induces sexual commitment of malaria parasites by antagonizing HP1-dependent gene silencing.

Author information

1
Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland.
2
University of Basel, 4003 Basel, Switzerland.
3
Department of Molecular Biology, Radboud University, 6525 GA Nijmegen, Netherlands.
4
Biozentrum, University of Basel, 4056 Basel, Switzerland.
5
Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland. till.voss@unibas.ch.

Abstract

Malaria is caused by Plasmodium parasites that proliferate in the bloodstream. During each replication cycle, some 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 in proliferating parasites. In this study, we identified Plasmodium falciparum gametocyte development 1 (GDV1) as an upstream activator of sexual commitment. We found that GDV1 targeted heterochromatin and triggered HP1 eviction, thus derepressing ap2-g Expression of GDV1 was responsive to environmental triggers of sexual conversion and controlled via a gdv1 antisense RNA. Hence, GDV1 appears to act as an effector protein that induces sexual differentiation by antagonizing HP1-dependent gene silencing.

PMID:
29590075
PMCID:
PMC6219702
DOI:
10.1126/science.aan6042
[Indexed for MEDLINE]
Free PMC Article

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