Histone deacetylase and associated chromatin components (HDACs)

Histone deacetylases (HDACs) and associated chromatin components are essential regulators of the epigenetic landscape, governing DNA accessibility for transcription [UniProt: P13569]. HDACs are enzymes that catalyze the removal of acetyl groups from lysine residues on histone tails, promoting a condensed chromatin state (heterochromatin) and transcriptional repression [PubMed: 22234955]. This target group also includes various co-repressor complexes (e.g., NuRD, CoREST) and chromatin-remodeling proteins that function alongside HDACs to modulate gene expression [PubMed: 24784545]. Dysregulation of these components is a hallmark of many cancers, leading to the silencing of tumor suppressor genes, and is also implicated in neurodegenerative and inflammatory disorders [PubMed: 28935956, PubMed: 21546610]. Pharmacological HDAC inhibitors (HDACis) induce histone hyperacetylation, which restores the expression of genes involved in cell cycle arrest, differentiation, and apoptosis [StatPearls: Histone Deacetylase Inhibitors]. Several HDACis, such as vorinostat and romidepsin, are FDA-approved for treating T-cell lymphomas and multiple myeloma, while ongoing research explores their efficacy in solid tumors and non-malignant conditions [FDA: Zolinza, Istodax].

Other names

HDACsLysine deacetylasesKDACsHistone deacetylase complexChromatin-modifying enzymes

Inhibition of histone deacetylase enzymes leads to increased acetylation of histone tails, resulting in a more open chromatin structure (euchromatin) and altered gene expression, typically inducing cell cycle arrest and apoptosis in cancer cells [StatPearls: Histone Deacetylase Inhibitors].