Class I and II zinc-dependent histone deacetylases (HDACs)

Class I and II zinc-dependent histone deacetylases (HDACs) are a family of enzymes that play a pivotal role in the epigenetic regulation of gene expression by removing acetyl groups from lysine residues on histones (UniProt, PubMed). This activity promotes a condensed chromatin state, typically leading to transcriptional repression of various genes, including tumor suppressors (NIH, PubMed). Beyond histones, these enzymes also deacetylate a wide array of non-histone proteins involved in cell cycle regulation, apoptosis, and signal transduction (PubMed, ResearchGate). Class I HDACs (1, 2, 3, and 8) are primarily nuclear and ubiquitously expressed, while Class II HDACs (4, 5, 6, 7, 9, and 10) exhibit tissue-specific expression and can shuttle between the nucleus and cytoplasm (NIH, PubMed). Dysregulation or overexpression of Class I and II HDACs is frequently observed in various cancers, where they contribute to the silencing of genes that control cell growth and survival (NIH, PubMed). Consequently, they have become significant therapeutic targets, with several HDAC inhibitors approved for the treatment of hematological malignancies like cutaneous T-cell lymphoma and multiple myeloma (Drugs.com, Wikipedia). These drugs typically work by chelating the zinc ion in the enzyme's active site, thereby restoring normal acetylation levels and inducing cell cycle arrest or apoptosis in malignant cells (NIH, PubMed). Ongoing research also explores their potential in treating neurodegenerative, inflammatory, and cardiovascular diseases (NIH, Wikipedia).

Other names

Histone deacetylasesZn2+-dependent HDACsClassical HDACsLysine deacetylasesKDACs

Inhibition of the catalytic activity of HDACs by chelating the zinc ion in the active site, leading to hyperacetylation of histones and non-histone proteins, which results in altered gene expression, cell cycle arrest, and apoptosis.