A Systematic Analysis of Myb domain–containing proteins in Toxoplasma gondii
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schwarz-schwarzd-phd-biology-2026-thesis .pdf
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Author(s)
Schwarz, Dominic
Advisor(s)
Lourido, Sebastian
Date Issued
February 2026
Publisher
Massachusetts Institute of Technology
Abstract
Apicomplexan parasites are a large and diverse clade of protists responsible for significant diseases of humans and animals. Central to the ability of these parasites to colonize their host and evade immune responses is an expanded repertoire of gene-expression programs that requires the coordinated action of complex transcriptional networks. DNA-binding proteins and chromatin regulators are essential orchestrators of apicomplexan gene expression that often act in concert. Although apicomplexan genomes encode various families of putative DNA-binding proteins, most remain functionally and mechanistically unexplored. In this thesis, I highlighted the versatile role of Myb domain–containing proteins in apicomplexan parasites as transcription factors and chromatin regulators. I explored the diversity of Myb domain structures and used phylogenetic analysis to identify common features across the phylum. Building on this framework, I systematically characterized the Myb protein family in Toxoplasma gondii. High-throughout tagging combined with conditional depletion revealed essential roles for multiple nuclear Myb proteins in parasite growth, cell division and developmental transitions. Transcriptional profiling uncovered diverse regulatory functions, with several Myb proteins showing strong homology to conserved chromatin regulators including ISWI, INO80, and SWI/SNF complexes. I defined the composition of two SWI/SNF complexes distinguished by mutually exclusive ATPases with homology to the widely conserved BRG1 and BRM. By integrating transcriptomics with a custom chromatin-profiling strategy, I demonstrated that TgBRG1 is essential for the timely transcription of genes during mitosis and cytokinesis, while TgBRM ensures global transcriptional competency and fidelity throughout the cell cycle and developmental transitions. These findings highlight the distinct, yet interdependent regulatory roles of TgBRG1 and TgBRM, shaped by their chromatin context, and uncover ancestral principles of chromatin regulation, offering new insights into the functional diversification of SWI/SNF complexes across eukaryotes.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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