Single cell expression and chromatin accessibility of the Toxoplasma gondii lytic cycle identifies AP2XII-8 as an essential ribosome regulon driver

Jingjing Lou, Yasaman Rezvani, Argenis Arriojas, Yihan Wu, Nachiket Shankar, David Degras, Caroline D. Keroack, Manoj T. Duraisingh, Kourosh Zarringhalam () and Marc-Jan Gubbels ()
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Jingjing Lou: Boston College
Yasaman Rezvani: University of Massachusetts Boston
Argenis Arriojas: University of Massachusetts Boston
Yihan Wu: Boston College
Nachiket Shankar: University of Massachusetts Boston
David Degras: University of Massachusetts Boston
Caroline D. Keroack: Harvard University
Manoj T. Duraisingh: Harvard University
Kourosh Zarringhalam: University of Massachusetts Boston
Marc-Jan Gubbels: Boston College

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Sequential lytic cycles driven by cascading transcriptional waves underlie pathogenesis in the apicomplexan parasite Toxoplasma gondii. This parasite’s unique division by internal budding, short cell cycle, and jumbled up classically defined cell cycle stages have restrained in-depth transcriptional program analysis. Here, unbiased transcriptome and chromatin accessibility maps throughout the lytic cell cycle are established at the single-cell level. Correlated pseudo-timeline assemblies of expression and chromatin profiles maps transcriptional versus chromatin level transition points promoting the cell division cycle. Sequential clustering analysis identifies functionally related gene groups promoting cell cycle progression. Promoter DNA motif mapping reveals patterns of combinatorial regulation. Pseudo-time trajectory analysis reveals transcriptional bursts at different cell cycle points. The dominant burst in G1 is driven largely by transcription factor AP2XII-8, which engages a conserved DNA motif, and promotes the expression of 44 ribosomal proteins encoding regulon. Overall, the study provides integrated, multi-level insights into apicomplexan transcriptional regulation.

Date: 2024
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DOI: 10.1038/s41467-024-51011-7

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