Date of Award
Bachelor of Science
Morgan Sammons , Ph.D.
Certain non-coding DNA sequences in the eukaryotic genome regulate gene expression. These non-coding regulatory regions, including promoters and enhancers, are controlled by the binding of multiple transcription factors which act together to regulate gene transcription. The number of potential transcription factor combinations regulating any gene presents a massive experimental challenge. One well-known transcription factor, p53, activates multiple transcription pathways involved in tumor suppression, primarily through engagement with enhancers. p53 is one member of a paralogous transcription factor family, which includes the factor p63. Whereas p53 is involved in tumor suppression, p63 is a transcription factor responsible for maintaining epithelial cell populations through its ability to bind to and regulate enhancers. p63 and p53 are often bound to the same enhancers in the genome, suggesting a more complex regulation than predicted by their canonical functions. We therefore aimed to better understand how genomic binding sequences and other factors regulate p53 and p63 activity at enhancers. Luciferase reporter gene assays were utilized to measure the transcriptional output of various p63 and p53 enhancers after genetically altering flanking DNA sequence motifs. We found that changing these flanking regions revealed core regulatory sequences that drive p53 and p63 transcriptional activity. We also determined that p63-bound enhancers, but not those bound by p53, had context-dependent activity. Depending on the cell type, these enhancers are active or inactive, with basal expression of p63 determining their activity. Our data provide new insight into the regulation of p53 family enhancers, and further work will lead to a better understanding of transcription factor activity and function at enhancers.
Kuang, Sylvia, "An Assessment of Combinatorial Transcription Factor Activity at p53 Enhancer Elements" (2019). Biological Sciences. 59.