Class I histone deacetylase (HDAC Class I) (HDAC Class I)

Class I histone deacetylases (HDACs) are a family of enzymes comprising HDAC1, HDAC2, HDAC3, and HDAC8 that play a pivotal role in the epigenetic regulation of gene expression (UniProt Consortium, 2024). These enzymes are primarily localized to the nucleus and function by removing acetyl groups from the epsilon-amino groups of lysine residues on histone tails, leading to chromatin condensation and transcriptional silencing (Seto & Yoshida, 2014). Beyond their action on histones, Class I HDACs also deacetylate numerous non-histone proteins, such as p53 and E2F1, thereby regulating cell cycle progression, apoptosis, and DNA repair mechanisms (Falkenberg & Johnstone, 2014). In many human cancers, Class I HDACs are overexpressed, which contributes to the aberrant silencing of tumor suppressor genes and promotes oncogenic transformation (West & Johnstone, 2014). Consequently, they have become significant therapeutic targets; several HDAC inhibitors, such as Vorinostat and Romidepsin, are FDA-approved for the treatment of cutaneous and peripheral T-cell lymphomas (NIH, 2023). Ongoing clinical research is also investigating the role of Class I HDAC inhibition in treating solid tumors, neurodegenerative diseases, and inflammatory conditions (Falkenberg & Johnstone, 2014). The development of isoform-selective inhibitors is a major focus to improve therapeutic efficacy and reduce the off-target toxicities associated with pan-HDAC inhibition (West & Johnstone, 2014).

Other names

HDAC1HDAC2HDAC3HDAC8RPD3-like histone deacetylasesClass I HDACs

Inhibition of the enzymatic removal of acetyl groups from lysine residues on histones and non-histone proteins, leading to increased acetylation, chromatin relaxation, and altered gene expression patterns (Seto & Yoshida, 2014).