Dissecting the role of PfAP2-G in malaria gametocytogenesis

Nat Commun. 2020 Mar 20;11(1):1503. doi: 10.1038/s41467-020-15026-0.

Abstract

In the malaria parasite Plasmodium falciparum, the switch from asexual multiplication to sexual differentiation into gametocytes is essential for transmission to mosquitos. The transcription factor PfAP2-G is a key determinant of sexual commitment that orchestrates this crucial cell fate decision. Here we identify the direct targets of PfAP2-G and demonstrate that it dynamically binds hundreds of sites across the genome. We find that PfAP2-G is a transcriptional activator of early gametocyte genes, and identify differences in PfAP2-G occupancy between gametocytes derived via next-cycle and same-cycle conversion. Our data implicate PfAP2-G not only as a transcriptional activator of gametocyte genes, but also as a potential regulator of genes important for red blood cell invasion. We also find that regulation by PfAP2-G requires interaction with a second transcription factor, PfAP2-I. These results clarify the functional role of PfAP2-G during sexual commitment and early gametocytogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems
  • Erythrocytes / parasitology
  • Gene Expression Regulation
  • Genes, Protozoan / genetics
  • Malaria / parasitology*
  • Malaria / transmission
  • Malaria, Falciparum / parasitology
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / growth & development*
  • Plasmodium falciparum / metabolism
  • Protozoan Proteins / blood
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / metabolism*
  • Transcription Factors / metabolism

Substances

  • Protozoan Proteins
  • Transcription Factors