deacetylases

Deacetylases are enzymes that remove acetyl groups from lysine residues on proteins. In chromatin, histone deacetylases (HDACs) repress gene transcription by restoring positive charge on histones and promoting tighter DNA–histone interactions. Many deacetylases act on non-histone substrates as well, regulating processes such as signaling, metabolism, and cytoskeletal dynamics.

Classification: In humans, deacetylases are grouped into four classes. Class I includes HDAC1, HDAC2, HDAC3, and HDAC8; Class II is subdivided into IIa (HDAC4, HDAC5, HDAC7, HDAC9) and IIb (HDAC6, HDAC10); Class III comprises the NAD+-dependent sirtuins (SIRT1-7); Class IV contains HDAC11. Classical HDACs (Classes I, II, IV) are zinc-dependent metalloproteins; class III sirtuins do not require zinc but use NAD+ as a co-substrate.

Function: HDACs regulate gene expression by removing acetyl groups from histones, leading to chromatin condensation and transcriptional repression. They also deacetylate many non-histone proteins, influencing DNA repair, cell cycle progression, differentiation, signaling, and metabolism. Localization varies: nuclear, cytoplasmic, or both.

Clinical relevance and inhibitors: Aberrant HDAC activity is linked to cancer, neurodegeneration, and metabolic disorders. Several HDAC inhibitors (HDACis) such as vorinostat, romidepsin, panobinostat, and belinostat are approved for certain cancers; research explores neuroprotective and anti-inflammatory applications. Inhibitors can have broad effects due to multiple substrates; selectivity and biological context matter.