A cascade of transcriptional repression determines sexual commitment and development in Plasmodium falciparum

This study identifies six new ApiAP2 members associated with gametocytogenesis in Plasmodium falciparum. PfAP2-G5 is crucial for both sexual commitment and development via regulation of the transcription of pfap2-g and/or its downstream target genes. PfAP2-G5 suppresses the expression levels of pfap2-g via binding to the upstream regulatory region directly or through recruitment to the exonic gene body involved in the maintenance of local heterochromatin structure.

• 1
  PfAP2-G5 suppresses the transcriptional activity of the pfap2-g gene via binding to both the upstream region and exonic gene body, preventing initiation of sexual commitment.
• 2
  PfAP2-G5 is essential for gametocyte maturation, and causes the down-regulation of pfap2-g and a set of early gametocyte genes activated by PfAP2-G prior to gametocyte development.
• 3
  Removal of the repressive effect of PfAP2-G5 through knockout disrupts the asexual replication cycle and promotes sexual commitment, but the gametocytes produced fail to mature fully.