Investigating the role of HMGNs in genome structure (2023)
Undergraduate: Rebecca Lewis
Faculty Advisor: Jill Dowen
Department: Biochemistry & Biophysics, Biology, Curriculum in Genetics and Molecular Biology
Regulation of gene expression is governed by proper organization of the genome. The histone landscape regulates the accessibility of DNA for gene expression, which is essential for proper cell function, yet the precise details of this system are not well understood. The High Mobility Group Nucleosome-binding proteins (HMGNs) are found on the genome at active sites that are marked by specific histone post-translational modifications (PTMs). HMGN1, HMGN2, and histone PTMs are known to localize to enhancers and promoters, but it is not yet known how these elements may interact or influence each other at shared sites to regulate gene expression. HMGNs bind to the acidic patch on the nucleosome disc face and have a tail that is suggested to interact with the histone tails. We hypothesize that HMGNs directly bind to histone PTMs present at enhancers and promoters through their C-terminal tail, affecting the deposition of active histone marks, which influences enhancer-promoter loops and gene expression. We produced expression plasmids containing the Hmgn coding sequences, allowing us to purify tailless and full-length HMGN proteins. With purified HMGN, we can directly test its binding ability to various histone PTMs as well as determine the role of the C-terminal tail in these interactions via nucleosome binding assays. By elucidating the role of HMGNs in histone PTM regulation, we will better understand the mechanisms of genome organization that control gene expression, which is important to understand the mechanisms of diseases such as cancer.
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