Identification of a novel AP2 transcription factor in zygotes with an essential role in Plasmodium ookinete development

PLoS Pathog. 2022 Aug 10;18(8):e1010510. doi: 10.1371/journal.ppat.1010510. eCollection 2022 Aug.


The sexual phase of Plasmodium represents a crucial step in malaria transmission, during which these parasites fertilize and form ookinetes to infect mosquitoes. Plasmodium development after fertilization is thought to proceed with female-stored mRNAs until the formation of a retort-form ookinete; thus, transcriptional activity in zygotes has previously been considered quiescent. In this study, we reveal the essential role of transcriptional activity in zygotes by investigating the function of a newly identified AP2 transcription factor, AP2-Z, in P. berghei. ap2-z was previously reported as a female transcriptional regulator gene whose disruption resulted in developmental arrest at the retort stage of ookinetes. In this study, although ap2-z was transcribed in females, we show that it was translationally repressed by the DOZI complex and translated after fertilization with peak expression at the zygote stage. ChIP-seq analysis of AP2-Z shows that it binds on specific DNA motifs, targeting the majority of genes known as an essential component of ookinetes, which largely overlap with the AP2-O targets, as well as genes that are unique among the targets of other sexual transcription factors. The results of this study also indicate the existence of a cascade of transcription factors, beginning with AP2-G, that proceeds from gametocytogenesis to ookinete formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Malaria* / genetics
  • Malaria* / parasitology
  • Plasmodium berghei* / metabolism
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zygote / metabolism


  • Protozoan Proteins
  • Transcription Factors

Grant support

MY, 17H01542; IK, 20K07462 and TN, 21K06986 were supported by Japan Society for the Promotion of Science,, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.