Investigating the role of HMGN proteins in genome organization (2024)

Undergraduates: Rebecca Lewis, Zhihan Gao, Riya Gohil

Faculty Advisor: Jill Dowen
Department: Biochemistry and Biophysics

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Genome organization regulates gene expression, which is essential for proper cell function. Both the histone landscape and Cohesin- and CTCF-mediated chromatin play a role in this genome organization. The molecular mechanisms that underlie these roles are not well understood. The High Mobility Group Nucleosome-binding proteins (HMGNs) are found on the genome at sites of active transcription that are found at DNA loop anchors and are marked by specific histone post-translational modifications (PTMs). HMGN1, HMGN2, Cohesin, CTCF, and specific histone PTMs are all known to localize to enhancers and promoters, but it is not yet known whether and how these elements may interact or influence each other at shared sites to regulate gene expression (Figure 1). Our study aims to investigate the link between Cohesin, CTCF, HMGNs, and the histone code. We examined the effects of loss of HMGN1 and HMGN2 in mESCs on gene expression and the genome-wide localization of Cohesin and CTCF. We investigated interactions between Cohesin, CTCF, and the HMGNs via co-Immunoprecipitation. Our findings show that HMGNs did not bind Cohesin or CTCF under high-stringency conditions. However, we saw differential expression of about 700 genes after the loss of HMGN1 and HMGN2. These results suggest that HMGNs may not play a role in the mechanisms of Cohesin-mediated chromatin looping, but instead may be involved in the regulation of nucleosome dynamics. Future investigation must be done to further illuminate the interplay between HMGNs and the histone code.