Fig. 3.

Parasite life cycle (A) and dynamic remodeling of the parasite nuclear architecture (B) during the asexual and sexual life stages. A) Sporozoites enter humans through an infected mosquito bite and subsequently establish an infection in the liver. Upon egress from the liver, the parasite replicates asexually inside red blood cells (intraerythrocytic developmental cycle; IDC). During this replication cycle, a small proportion of parasites will commit to sexual differentiation into male and female gametocytes that can be taken up by a mosquito. Sexual reproduction takes place inside the mosquito midgut and ultimately results in the formation of sporozoites that can be transmitted to a new human host. B) Centromeric (orange circles) and telomeric (grey circles) clusters remain localized to the nuclear periphery at all stages. Telomere regions as well as the internally located var genes (red circle) are located within the repressive center(s) (yellow). The remaining genome (light grey) is largely present in a transcriptionally permissive euchromatin state. Extensive remodeling of the nucleus takes place as the parasite progresses through the ring, trophozoite, schizont and gametocyte stages. In the transition from the relatively inactive ring stage to the transcriptionally active trophozoite stage, the nuclear size and the number of nuclear pores increase. Invasion genes that localize to the parasite repressive center become active at the schizont stage and are moved away from the heterochromatin environment. Loss of interaction between the repressive cluster and pfap2-g transcription factor is observed at the gametocyte stages.