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Nat Commun ; 12(1): 116, 2021 01 07.
Article in English | MEDLINE | ID: mdl-33414462

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.


Subject(s)
Cell Cycle/physiology , Cell Division/physiology , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Toxoplasma/genetics , Toxoplasma/physiology , Cell Proliferation , Centrosome , DNA Replication , Gene Expression Regulation , Gene Knockdown Techniques , Humans , Organisms, Genetically Modified , Transcription Factors/genetics , Transcription Factors/metabolism
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