Chemical Tools for Investigating the Tandem PHD Finger-Bromodomain Cassette of TRIM Proteins

If human DNA was laid out end to end it could be wrapped around the earth several million times and yet somehow it still fits in our bodies. This is because our DNA is tightly wrapped around proteins called histones. Natural chemical modifications on the histones determine how our genetic code is read by acting as a signal to 'reader' proteins, to switch a gene on or off in response to environmental factors. For this project we are interested in specific readers belonging to the TRIM protein family - a large class of ubiquitous proteins that are involved in numerous biological processes including innate immunity, DNA repair, and cell proliferation. Several TRIMs contain a region called the 'tandem PHD finger-bromodomain cassette' which can read specific combinations of histone modifications; however, the biological consequences of this readout are unknown. In this project we aim to develop chemical tools that can be used to investigate the
effects of blocking the PHD finger and bromodomain in TRIM proteins. The results of this study could help improve our understanding of how the PHD finger and bromodomain co-operate and their roles within TRIM proteins. This information would be useful for developing new pharmaceutical strategies pharmaceutical strategies in the future.