GDV1 induces sexual commitment of malaria parasites by antagonizing HP1 dependent gene silencing
Sexual development in Plasmodium Malaria causing parasites (Plasmodium) have complex life histories in the tissues of humans. For the most part, the parasites focus their efforts on replication within the human host cells. However, occasionally, some replicating cells release gametes into the bloodstream, which are picked up by biting mosquitoes. Filarsky et al. discovered that the Plasmodium parasite keeps the production of gametes under tight epigenetic control using heterochromatin protein 1 (HP1) Plasmodium gametocytogenesis is initiated when HP1 is evicted from upstream of gamete specific genes by gametocyte development 1 (GDV1) protein. GDV1 is in turn regulated by its antisense RNA. What triggers GDV1 expression remains unclear. Elucidating this pathway could provide a target for interrupting malaria transmission. Science, this issue p. 1259 Plasmodium replication is interrupted for gamete production by eviction of a heterochromatin binding protein upstream of the relevant genes. 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.
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