Mechanisms of triggering malaria gametocytogenesis by AP2-G

• Published in: Parasitology international 2021-10, Vol.84, p.102403-102403, Article 102403
• Main Authors: Yuda, Masao, Kaneko, Izumi, Murata, Yuho, Iwanaga, Shiroh, Nishi, Tsubasa
• Format: Article
• Language: English
• Subjects: AP2-G; Gametocyte; Malaria; Transcription factor
• ISSN: 1383-5769; 1873-0329
• DOI: 10.1016/j.parint.2021.102403

The transcription factor (TF) AP2-G is essential for gametocytogenesis in the malaria parasite; however, it remains unclear if AP2-G determines commitment to sexual stage development fate in the schizont stage, or whether AP2-G directly initiates sexual stage differentiation and development beginning in the late-trophozoite stage. In this study, we addressed this issue by investigating the expression profile of AP2-G and determining genome-wide target genes in Plasmodium berghei. Fluorescence microscopy showed that AP2-G expression was first observed in the parasite 12 h after erythrocyte invasion and peaked at 18 h when sexual features were first manifested in early gametocytes. Expression of AP2-G decreased with manifestation of sex-specific features. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) was performed at peak AP2-G expression and identified over 1000 binding sites in the genome. The main binding motif of the TF predicted from the binding sites was GTACNY. Predicted targets contained a number of genes related to protein biogenesis, suggesting that AP2-G plays a role in establishing a cellular basis required for sexual differentiation. AP2-G binding sites also existed upstream of gametocyte-specific TFs, namely AP2-G2, AP2-FG, and AP2-G itself. Furthermore, the target contained two AP2 TF-related genes. Disruption of these genes resulted in the arrest of ookinete development. These results suggest another role of AP2-G: activating a transcriptional cascade to promote conversion into early gametocytes. Taken together, AP2-G is involved not in establishing sexual commitment of schizonts, but rather in triggering the initiation of differentiation and the early development of gametocytes in the late trophozoite stage. [Display omitted] •AP2-G is a transcription factor essential for gametocytogenesis.•It remains elusive whether AP2-G is involved in commitment or sexual differentiation.•Here, we report in P. berghei that AP2-G is involved in the latter process.