Department of Biology, Boston College, Chestnut Hill, MA, USA.
Department of Mathematics, University of Massachusetts Boston, Boston, MA, USA.
Nat Commun. 2024 Aug 28;15(1):7419. doi: 10.1038/s41467-024-51011-7.
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.
层叠转录波驱动的连续裂解周期是顶复门寄生虫刚地弓形虫发病机制的基础。该寄生虫独特的内芽殖分裂、短细胞周期和混乱的经典定义的细胞周期阶段限制了深入的转录程序分析。在这里，在单细胞水平上建立了整个裂解细胞周期的无偏转录组和染色质可及性图谱。表达和染色质图谱的相关拟时组装确定了促进细胞分裂周期的转录与染色质水平转换点。顺序聚类分析确定了促进细胞周期进展的功能相关基因群。启动子 DNA 基序作图揭示了组合调控的模式。拟时轨迹分析揭示了不同细胞周期点的转录爆发。G1 中的主要爆发主要由转录因子 AP2XII-8 驱动，它结合保守的 DNA 基序，并促进 44 个核糖体蛋白编码调控子的表达。总的来说，该研究提供了对顶复门转录调控的综合、多层次的见解。
