Discussion

Bromodomains (BRDs) are protein modules that specifically recognize and bind to acetylated lysine residues on histone tails and are referred to as epigenetic readers. Epigenetics is a growing area of interest in terms of targeting a number of disease states e.g. oncology, CNS, inflammation and cardiovascular disease. This target class has been shown to be druggable with small molecules which affect the BET family and hence there is a growing interest in understanding other bromodomain families in terms of both biology and drugability.
Using a number of different approaches from protein to primary cells and in collaboration with UCL we have used small molecules to increase our understanding and build our knowledge around type IV bromodomains. This has involved generating protein reagents and in vitro assays along with using primary cells from tissue to analyse gene expression and the effects of small molecules on cytokines. Our data has shown that BRPF1b and BRD9 appear to be of specific interest in inflammatory disease and associated indications.