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.

Automated summary

Histone deacetylases (HDACs) are epigenetic enzymes that regulate gene expression and are influenced by cellular metabolism. The crosstalk between metabolism and histone acetylation impacts various biological processes. The use of systems biology methods can help uncover the interactions between metabolism, HDACs, and HDAC inhibitors, leading to the identification of potential biomarkers and therapeutic targets.