Plasmodium transcription repressor AP2-O3 regulates sex-specific identity of gene expression in female gametocytes

EMBO Rep. 2021 May 5;22(5):e51660. doi: 10.15252/embr.202051660. Epub 2021 Mar 4.


Male and female gametocytes are sexual precursor cells essential for mosquito transmission of malaria parasite. Differentiation of gametocytes into fertile gametes (known as gametogenesis) relies on the gender-specific transcription program. How the parasites establish distinct repertoires of transcription in the male and female gametocytes remains largely unknown. Here, we report that an Apetala2 family transcription factor AP2-O3 operates as a transcription repressor in the female gametocytes. AP2-O3 is specifically expressed in the female gametocytes. AP2-O3-deficient parasites produce apparently normal female gametocytes. Nevertheless, these gametocytes fail to differentiate into fully fertile female gametes, leading to developmental arrest in fertilization and early development post-fertilization. AP2-O3 disruption causes massive upregulation of transcriptionally dormant male genes and simultaneously downregulation of highly transcribed female genes in the female gametocytes. AP2-O3 targets a substantial proportion of the male genes by recognizing an 8-base DNA motif. In addition, the maternal AP2-O3 is removed after fertilization, which is required for the zygote to ookinete development. Therefore, the global transcriptional repression of the male genes in the female gametocytes is required for safeguarding female-specific transcriptome and essential for the mosquito transmission of Plasmodium.

Keywords: Plasmodium; gametocyte; gametogenesis; gender-specific; transcription repressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Gametogenesis / genetics
  • Male
  • Plasmodium berghei*
  • Plasmodium falciparum* / genetics
  • Protozoan Proteins / genetics
  • Transcription Factors / genetics
  • Transcriptome


  • Protozoan Proteins
  • Transcription Factors