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  • 1. Holub, Ashton Identifying regulatory mechanisms for evolutionarily conserved StARkin domains of plant transcription factors and human tumor suppressors.

    Doctor of Philosophy, The Ohio State University, 2022, Molecular Genetics

    StARkin domains are a superfamily of structurally conserved ligand binding domains found in all the domains of life. These domains use a diverse set of mechanisms to regulate the activity of multidomain proteins they are integrated into, will identified roles in mediating homo/heteromeric interactions, subcellular localization, protein stability, and protein turnover. One subfamily of StARkin domains, StAR-related lipid transfer (START) domains, is found in both plant CLASS III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIPIII) transcription factors (TFs) and human deleted in liver cancer (DLC) tumor suppressor genes. Both families of proteins have critical roles in development, however, roles of the START domain in regulating the activity of either of these protein families is largely unknown. In Arabidopsis thaliana, phylogenetic analysis of HD-ZIPIII paralogs shows divergent activity stemming from coding sequence divergence, separating the five HD-ZIPIII paralogs into two sister clades, the REVOLUTA clade and the CORONA clade. HD-ZIPIII paralogs have redundant developmental activities, with distinct and antagonist effects between these sister clades. Preliminary work in our lab investigating the START domain of a representative REVOLUTA clade paralog, PHABULOSA (PHB), shows that the START domain is required for the developmental activity of PHB and regulates homodimerization, DNA-binding, and transactivation potential. In this study, I present the divergent activity of a representative CORONA clade paralog, CORONA (CNA), mediated by its START domain. We identify the target genes of PHB and CNA, highlighting overlapping, distinct, and antagonist regulation of target genes representative of their redundant developmental roles with distinct, and antagonist effects on each other. Additionally, using domain swap experiments, I identify two new properties of the CNA START domain in modulating the behavior of the binding sites of CNA, as well as modulating transactivation / tra (open full item for complete abstract)

    Committee: Aman Husbands (Advisor); Jay Hollick (Committee Member); Mark Seeger (Committee Member); Ruben Petreaca (Committee Member); Amanda Bird (Committee Member) Subjects: Biology; Molecular Biology; Plant Biology