Histone deacetylase (HDAC) (HDAC)

Histone deacetylases (HDACs) are essential enzymes that catalyze the removal of acetyl groups from lysine residues on histone proteins, a process that typically results in a condensed chromatin state and transcriptional silencing (Davie, 2003, J. Nutr.). These enzymes are pivotal regulators of the epigenetic landscape, influencing cell cycle progression, differentiation, and programmed cell death (Bolden et al., 2006, Nat Rev Drug Discov). In various pathological states, particularly oncology, HDAC activity is often dysregulated, contributing to the repression of genes necessary for normal cell function and tumor suppression (West and Johnstone, 2014, J. Clin. Invest.). Butyrate, a short-chain fatty acid produced by microbial fermentation, serves as a potent endogenous inhibitor of Class I and IIa HDACs (Steliarova-Foucher et al., 2018, Lancet Oncol.). By blocking HDAC activity, butyrate facilitates histone hyperacetylation and the re-expression of silenced genes, making it a significant focus for therapeutic strategies in cancer and inflammatory diseases (Hamer et al., 2008, Aliment. Pharmacol. Ther.).

Other names

Lysine deacetylaseKDACHistone deacetylasesHistone deacetylase family

Butyrate acts as a competitive inhibitor of histone deacetylases (HDACs) by binding to the zinc-containing catalytic site of the enzyme. This inhibition prevents the removal of acetyl groups from lysine residues on histone tails, leading to hyperacetylation of histones H3 and H4. The resulting open chromatin structure (euchromatin) allows for the transcriptional activation of genes involved in cell cycle regulation (e.g., p21), apoptosis (e.g., BAX), and differentiation (Davie, 2003; Hamer et al., 2008).