Model
Digital Document
Publisher
Florida Atlantic University
Description
Epigenetic dysregulation has been implicated in oncogenesis, with post-translational histone modifications being linked to cancer progression. WSTF/BAZ1B forms chromatin-remodeling complexes with other proteins and lowers cancer survival outcomes. Treatment resistance causes >90 % of all cancer deaths. In particular, cancers develop tolerance to cisplatin-induced genotoxicity. It is hypothesized that the BAZ1B bromodomain, PHD finger, and DDT domain recognize epigenetic modifications, contributing to cisplatin resistance in cancers. To test this, the domains were expressed in Rosetta 2 BL21(DE3) and Rosetta 2 BL21(DE3) PLysS Escherichia coli strains. Soluble proteins were extracted, purified, and then analyzed using pulldown assays and modified histone peptide arrays. The DDT and PHD finger domains were found to bind to specific histone modifications with the DDT domain also displayed DNA-binding properties. Some of the identified histone modifications have known roles/correlations in normal and cancer cells, implicating BAZ1B as an agent in oncogenesis, treatment resistance, and as a therapeutic target.
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