A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle

Cell Host Microbe. 2017 Jan 11;21(1):11-22. doi: 10.1016/j.chom.2016.12.003.


A family of apicomplexa-specific proteins containing AP2 DNA-binding domains (ApiAP2s) was identified in malaria parasites. This family includes sequence-specific transcription factors that are key regulators of development. However, functions for the majority of ApiAP2 genes remain unknown. Here, a systematic knockout screen in Plasmodium berghei identified ten ApiAP2 genes that were essential for mosquito transmission: four were critical for the formation of infectious ookinetes, and three were required for sporogony. We describe non-essential functions for AP2-O and AP2-SP proteins in blood stages, and identify AP2-G2 as a repressor active in both asexual and sexual stages. Comparative transcriptomics across mutants and developmental stages revealed clusters of co-regulated genes with shared cis promoter elements, whose expression can be controlled positively or negatively by different ApiAP2 factors. We propose that stage-specific interactions between ApiAP2 proteins on partly overlapping sets of target genes generate the complex transcriptional network that controls the Plasmodium life cycle.

Keywords: Apetala 2; ap2-l; ap2-o; ap2-o2; ap2-o3; ap2-o4; ap2-sp; ap2-sp2; ap2-sp3; oocyst.

MeSH terms

  • Animals
  • Anopheles / parasitology
  • Apicomplexa / genetics
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Knockout Techniques
  • Life Cycle Stages / genetics*
  • Malaria / parasitology
  • Malaria / transmission*
  • Mice
  • Oocysts / cytology
  • Plasmodium berghei / genetics*
  • Plasmodium berghei / growth & development
  • Protein Domains / genetics*
  • Protein Domains / physiology
  • Protozoan Proteins / genetics*


  • DNA-Binding Proteins
  • Protozoan Proteins