TgAP2IX-5 is a key transcriptional regulator of the asexual cell cycle division in Toxoplasma gondii
Asma S. Khelifa, Cecilia G. Sánchez, Kevin Lesage, Ludovic Huot, Thomas Mouveaux, Pierre Péricard, Nicolas Barois, Hélène Touzet, Guillemette Marot, Emmanuel Roger, Mathieu Gissot
Abstract
Apicomplexan parasites have evolved efficient and distinctive strategies for intracellular replication where the timing of emergence of the daughter cells (budding) is a decisive element. However, the molecular mechanisms that provide the proper timing of parasite budding remain unknown. Using Toxoplasma gondii as a model Apicomplexan, we identified a master regulator that controls the timing of the budding process. We show that an ApiAP2 transcription factor, TgAP2IX-5, controls cell cycle events downstream of centrosome duplication. TgAP2IX-5 binds to the promoter of hundreds of genes and controls the activation of the budding-specific cell cycle expression program. TgAP2IX-5 regulates the expression of specific transcription factors that are necessary for the completion of the budding cycle. Moreover, TgAP2IX-5 acts as a limiting factor that ensures that asexual proliferation continues by promoting the inhibition of the differentiation pathway. Therefore, TgAP2IX-5 is a master regulator that controls both cell cycle and developmental pathways.