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

Class I and IV histone deacetylases (HDACs) are a specific subset of the classical zinc-dependent HDAC family, encompassing HDAC1, 2, 3, and 8 (Class I) and HDAC11 (Class IV). These enzymes are primarily localized within the cell nucleus, where they play a fundamental role in epigenetic regulation by removing acetyl groups from lysine residues on histone proteins (UniProt, 2024). This deacetylation process promotes a condensed chromatin structure, effectively silencing the transcription of various genes involved in the cell cycle, differentiation, and programmed cell death.\n\nIn many human malignancies, Class I and IV HDACs are frequently overexpressed or dysregulated, contributing to the suppression of tumor suppressor genes and the maintenance of the oncogenic phenotype (PubMed: 22510408). Therapeutic agents targeting these enzymes, such as the FDA-approved romidepsin or the investigational mocetinostat, act by inhibiting the catalytic zinc site, leading to histone hyperacetylation and the restoration of normal gene expression patterns (NIH, 2023). While these inhibitors have shown significant clinical promise, particularly in hematological cancers, their clinical utility is often balanced against systemic toxicities like myelosuppression and potential cardiotoxicity (StatPearls, 2023).

Other names

Class I and IV HDACsZinc-dependent histone deacetylases (Class I and IV)HDAC Class I/IV

Inhibition of the zinc-dependent catalytic site of Class I and IV histone deacetylases, leading to increased acetylation of histones and non-histone proteins, which promotes open chromatin structure and alters gene transcription (PubMed: 18413728, StatPearls: NBK559020).