Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity

This study provided the first step in identifying multiple bioactive compound HDAC inhibitors. Taken together, this report sets the stage for future exploration of these bioactive compounds as epigenetic regulators to potentially ameliorate chronic disease.

Using class-specific HDAC substrates, we screened 131 natural compounds for HDAC activity in bovine cardiac tissue. From this screen, we identified 18 bioactive compound HDAC inhibitors. Using our class-specific HDAC substrates, we next screened these 18 bioactive compounds against recombinant HDAC proteins. Consistent with inhibition of HDAC activity, these compounds were capable of inhibiting activity of individual HDAC isoforms. Lastly, we report that treatment of H9c2 cardiac myoblasts with bioactive HDAC inhibitors was sufficient to increase lysine acetylation as assessed via immunoblot.