Characterizing Interactions of the Sox2 and LEF1 Transcription Factors with Non-B-Form Nucleic Acids

Undergraduate Honors Thesis

Citations

Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/3t945s014

Abstract

Transcription factors have been increasingly found to directly interact with a broad range of nucleic acids distinct from their canonical targets of B-form DNA. These interactions play roles in the regulation of gene expression that remain poorly understood to date. HMGB proteins are one such family of transcription factors that have been repeatedly implicated in alternative regulatory roles via their ability to associate with a diverse set of nucleic acid structures. We hypothesize that these transcription factors may have the capability to bind nucleic acid targets with some form of structural selectivity. Specifically, we examine the capabilities of Sox2 to bind internally bulged RNA hairpins and investigate the possibility of Sox2 and LEF1 directly targeting G-quadruplex structures in the genome. We find that, both, Sox2 and LEF1 associate with G-quadruplexes in the genome and posit that these interactions are likely relevant for the biology of these proteins. Furthermore, we find that Sox2 binds genomic G-quadruplexes with high affinity in vitro and develop the framework for an in vitro workflow to thoroughly assess these interactions.

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