Dissecting the role of PfAP2-G in malaria gametocytogenesis

• Published in: Nature communications 2020-03, Vol.11 (1), p.1503-1503, Article 1503
• Main Authors: Josling, Gabrielle A., Russell, Timothy J., Venezia, Jarrett, Orchard, Lindsey, van Biljon, Riëtte, Painter, Heather J., Llinás, Manuel
• Format: Article
• Language: English
• Subjects: 13; 13/106; 38/15; 38/39; 38/61; 631/136/142; 631/208/200; 631/250/255/1629; 631/337/572; Binding sites; Cell fate; Conversion; CRISPR-Cas Systems; Deoxyribonucleic acid; DNA; Erythrocytes; Erythrocytes - parasitology; Gametocytes; Gene expression; Gene Expression Regulation; Genes; Genes, Protozoan - genetics; Genomes; Humanities and Social Sciences; Malaria; Malaria - parasitology; Malaria - transmission; Malaria, Falciparum - parasitology; multidisciplinary; Multiplication; Occupancy; Parasites; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - growth & development; Plasmodium falciparum - metabolism; Protozoan Proteins - blood; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Science; Science (multidisciplinary); Sex differentiation; Target recognition; Transcription factors; Transcription Factors - metabolism; Vector-borne diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15026-0

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. The transcription factor PfAP2-G is a key determinant of sexual commitment in Plasmodium falciparum . Here, Josling et al. define the transcriptional regulatory network of PfAP2-G by identifying its DNA binding sites genome-wide, which vary depending on the route of sexual conversion and rely on interactions with the PfAP2-I transcription factor.