Context-dependent activity of an essential transcription factor

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Multicellular organisms acquire their complex shapes through carefully controlled developmental processes. Key regulators of plant development include a class of proteins called transcription factors, which coordinate the specificity and function of plant cells and tissues. The action of some transcription factors are limited to only a few cells or a subset of tissues, but there are other factors that play key roles in a large number of developing tissues. This raises an interesting biological question: how can the same transcription factor generate different developmental outcomes? This project answers the question by identifying how the same transcription factor can serve different functions in various cells and tissues. The project combines techniques of genetics and biochemistry, including advances in high-resolution mapping of protein-protein interactions. Central to this proposal is the inclusion of students traditionally excluded from research-intensive insitituions. At The Ohio State University (OSU), this is manifested in Black students and students-of-color being overrepresented at OSU regional campuses, where research opportunities are limited. To mitigate this problem, undergraduates will be brought to the OSU Columbus main campus, provided food and lodging, paid a stipend, and enrolled in a 100-student consortium consolidating the various concurrent summer research programs. This pipeline broadens participation of traditionally excluded groups by eliminating the unfair choice between working a summer job and exploring research as a career.Biological development results from tightly controlled gene expression driven by the activity of transcription factors (TFs). TFs have been repeatedly coopted throughout evolution to regulate key developmental advances, in part because their outputs vary depending on developmental context. Mechanisms that generate these context-dependent readouts remain largely unknown, and this knowledge gap is particularly large in the plant kingdom. This gap will be addressed using CLASS III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIPIII) TFs as a model. HD-ZIPIII proteins are a particularly attractive model as they regulate a broad range of essential developmental processes, acting in tissues and organs ranging from meristems to roots to lateral organs. In addition, HD-ZIPIII protein architecture includes a StAR-related lipid transfer (START) domain. START domains are typically activated by lipophilic ligands and often mediate protein-protein interactions, presenting possible mechanisms to generate context-dependent activity. This proposal will test the genetic consequences and functional partnerships of the representative HD-ZIPIII PHABULOSA (PHB) in two functionally-distinct cell types: the indeterminate cells of the shoot apical meristem and the determinate cells of the adaxial side of leaves. Experiments including global genomic profiling and proximity labeling will identify meristem- and leaf-specific PHB gene regulatory networks and interactomes, and test whether the START domain plays a role in generating context-dependent activity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.