Metabolism, HDACs, and HDAC Inhibitors: A Systems Biology Perspective.

Histone deacetylases (HDACs) are epigenetic enzymes that play a central role in gene regulation and are sensitive to the metabolic state of the cell. The cross talk between metabolism and histone acetylation impacts numerous biological processes including development and immune function. HDAC inhibitors are being explored for treating cancers, viral infections, inflammation, neurodegenerative diseases, and metabolic disorders. However, how HDAC inhibitors impact cellular metabolism and how metabolism influences their potency is unclear. Discussed herein are recent applications and future potential of systems biology methods such as high throughput drug screens, cancer cell line profiling, single cell sequencing, proteomics, metabolomics, and computational modeling to uncover the interplay between metabolism, HDACs, and HDAC inhibitors. The synthesis of new systems technologies can ultimately help identify epigenomic and metabolic biomarkers for patient stratification and the design of effective therapeutics.