Histone deacetylase 1 (HDAC1) (HDAC1)

Histone deacetylase 1 (HDAC1) is a critical Class I enzyme that functions as the catalytic core of several major co-repressor complexes, including Sin3, NuRD, and CoREST (UniProt P50851). It is the primary human ortholog of the yeast Rpd3 protein; the term Rpd3L refers to the specific "large" complex in yeast, analogous to the human Sin3 complex, which targets deacetylation activity to gene promoters (PMID: 9707565). By removing acetyl groups from lysine residues on histone tails, HDAC1 promotes a condensed chromatin state and transcriptional repression of genes involved in the cell cycle and apoptosis (PubMed: 10406465). In various malignancies, HDAC1 is frequently overexpressed or misregulated, leading to the silencing of tumor suppressor genes and promotion of oncogenesis (Cancer Research, 2020). Therapeutic targeting of HDAC1 involves small-molecule inhibitors that typically chelate the zinc ion in the enzyme's active site, resulting in histone hyperacetylation and the re-expression of genes like p21 (PubChem, 2024). Several HDAC inhibitors, such as Vorinostat and Romidepsin, are FDA-approved for treating T-cell lymphomas, while others like Givinostat have been approved for Duchenne muscular dystrophy, with ongoing research into their potential for neurodegenerative and inflammatory conditions (StatPearls, 2023).

Other names

Rpd3RPD3LRPD3L1HD1Histone deacetylase 1 complexSin3-HDAC complexReduced potassium dependency 3

Inhibition of catalytic deacetylation activity via zinc-chelation in the enzyme active site, preventing the removal of acetyl groups from lysine residues on histones and non-histone proteins, which leads to chromatin relaxation and transcriptional reactivation of silenced genes.