Histone deacetylase class I enzyme (HDAC class I)

Histone deacetylase class I enzymes are a subgroup within the larger family of histone deacetylases. These zinc-dependent enzymes catalyze the removal of acetyl groups from ε-N-acetyl lysine residues on both core histones and numerous non-histone proteins. By removing these acetyl groups from chromatin-associated proteins—primarily on lysine residues—they promote chromatin condensation and transcriptional repression. Class I members include four main human isoforms: HDAC1, HDAC2, HDAC3, and HDAC8. Beyond their canonical role in gene silencing through chromatin remodeling, they also regulate diverse cellular processes by modifying non-histone substrates involved in cell cycle progression, apoptosis regulation, DNA repair mechanisms, signal transduction pathways such as Notch signaling, among others. Dysregulation or overexpression is implicated in cancer development/progression; thus they have become validated therapeutic targets for anticancer drug development. Several small-molecule inhibitors have been developed that selectively inhibit these enzymes' activity—leading to re-expression of silenced genes critical for growth arrest or apoptosis—and some have received regulatory approval for use against hematologic malignancies.

Other names

HDAC class IClass I histone deacetylaseHistone deacetylase 1/2/3/8 (HDAC1, HDAC2, HDAC3, HDAC8 are the main human class I isoforms)

Drugs targeting this molecule typically act as histone deacetylase inhibitors, blocking the removal of acetyl groups from lysine residues on histones and non-histone proteins. This leads to increased acetylation, relaxed chromatin structure, reactivation of silenced genes (including tumor suppressors), cell cycle arrest, apoptosis induction, and inhibition of cancer cell proliferation.