Class I and Class II histone deacetylases (HDACs) (Class I/II HDACs)

Class I and Class II histone deacetylases (HDACs) are a group of enzymes responsible for the removal of acetyl groups from the ε-amino groups of lysine residues located on the amino-terminal tails of histones and various non-histone proteins (UniProt, 2023). This deacetylation typically results in a more condensed chromatin state, leading to the transcriptional repression of target genes (PubMed, PMC3433950). Class I HDACs (HDAC1, 2, 3, and 8) are primarily located in the nucleus and are essential for cell proliferation and survival, while Class II HDACs (HDAC4, 5, 6, 7, 9, and 10) exhibit tissue-specific expression and can shuttle between the nucleus and cytoplasm (StatPearls, NBK559112). In many cancers, HDACs are overexpressed or aberrantly recruited to promoters, causing the silencing of tumor suppressor genes and contributing to oncogenesis (NIH, 2021). Pharmacological inhibition of these enzymes by HDAC inhibitors, such as Vorinostat and Panobinostat, leads to histone hyperacetylation, re-expression of silenced genes, and induction of cell cycle arrest or apoptosis in malignant cells (PubChem, 2024). Beyond oncology, these enzymes are being investigated as targets for neurodegenerative, inflammatory, and cardiovascular diseases due to their broad regulatory roles in cellular homeostasis.

Other names

HDACsHistone deacetylase familyLysine deacetylasesKDACsClass I HDACsClass II HDACs

Inhibition of the enzymatic activity of histone deacetylases, leading to hyperacetylation of histones and non-histone proteins, which promotes open chromatin structure and modulates the transcription of genes involved in cell growth, differentiation, and apoptosis (PubMed, PMC3433950).