A MultiOmics time-resolved systems map of gene regulation in Toxoplasma gondii
Understanding how T. gondii builds an invasion-competent cell has been limited by its rapid, asynchronous division cycle, incomplete gene function annotation, and studies that have examined one regulator or complex at a time. Here, we placed acute perturbation of 21 transcriptional and epigenetic factors, promoter occupancy, chromatin accessibility, and molecular validation on a common single-cell clock. The resulting consensus map links the lytic-cycle programs to candidate activating and repressive inputs, organizes genes into 108 co-regulated communities, and nominates regulatory partnerships that would not have emerged from any single data type. The work bridges three longstanding gaps: it resolves perturbation responses in cell-cycle time, distinguishes promoter occupancy from perturbation-linked regulation, and turns a large multidimensional dataset into an experimentally navigable map. We indeed confirmed known factor interactions such as MORC/HDAC3 and recovered combinations such as the Cdc5/SNIP1 and DMAP1/EPL1 as coregulatory nodes (that in other systems have been described to cooperate). Furthermore, we discovered a novel apicomplexan specific combination of AAF1/AP2XI-5 that provides mechanistic insights of the unique AP2 transcription factor family.
Authors
- Jiahong Li (ORCID: https://orcid.org/0000-0002-9687-0101)
- Gretchen Diffendall (ORCID: https://orcid.org/0000-0002-0783-517X)
- Lee S. Izhaki-Tavor (ORCID: https://orcid.org/0000-0002-7520-7984)
- Kourosh Zarringhalam (ORCID: https://orcid.org/0000-0002-5108-8108)
- Mélissa Léger-Abraham (ORCID: https://orcid.org/0000-0001-9374-0718)
- Marc‐Jan Gubbels (ORCID: https://orcid.org/0000-0002-2769-8600)
- Eranthie Weerapana (ORCID: https://orcid.org/0000-0002-0835-8301)
- Nachiket Shankar (ORCID: https://orcid.org/0009-0004-9785-3997)
- Argenis Arriojas (ORCID: https://orcid.org/0000-0002-0479-1300)
- Manoj T. Duraisingh (ORCID: https://orcid.org/0000-0001-8534-5515)
- Pamodya Pamunuwa (ORCID: https://orcid.org/0000-0002-1045-3308)
- Yihan Wu (ORCID: https://orcid.org/0009-0005-0155-8887)
- Shalini Aggarwal (ORCID: https://orcid.org/0000-0002-5951-2102)
- Prarthana Prathap
- Omar Graia (ORCID: https://orcid.org/0009-0004-8115-1501)
- Prince Oppong (ORCID: https://orcid.org/0009-0009-4147-1611)
- Jingjing Lou (ORCID: https://orcid.org/0000-0002-3304-454X)
- Shreya Dua (ORCID: https://orcid.org/0009-0006-1801-3805)
Institutions
- Boston College (US)
- Harvard University (US)
- University of Massachusetts Boston (US)
- Acton-Boxborough Regional High School (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-10-30
- DOI
- https://doi.org/10.64898/2026.10.29.762658
- Primary Topic
- Toxoplasma gondii Research Studies
- Type
- preprint
Funders
- National Institutes of Health