Histone deacetylase class I and class II (HDACs class I and II)

Histone deacetylases class I and class II are families of zinc-dependent enzymes that catalyze the removal of acetyl groups from lysine residues in histone tails and on many non-histone proteins. This enzymatic deacetylation leads to chromatin condensation, transcriptional repression, and broad changes in cell function. Class I HDACs (HDAC1, HDAC2, HDAC3, HDAC8) are predominantly nuclear and have high catalytic activity, whereas class II HDACs (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, HDAC10) can shuttle between cytoplasm and nucleus and often require complex formation for full activity. Both are key regulators of cell cycle, differentiation, apoptosis, and signal transduction, and dysregulation contributes to cancer and other diseases. HDACs are highly druggable targets; multiple drugs inhibit their zinc-dependent catalytic domains, reversing epigenetic gene silencing. Therapeutic HDAC inhibition can induce cell death in cancer, promote neuronal survival, and modulate immune responses but comes with toxicity risks due to their central roles in cell biology.

Other names

HDACsClass I HDACClass II HDACHistone deacetylaseHistone deacetylase family

HDAC inhibition by chelation of the Zn2+ ion in the active site (most small molecules inhibit by binding to the zinc-dependent catalytic domain, preventing deacetylation); Chromatin relaxation and transcriptional activation (HDAC inhibitors cause histone hyperacetylation, leading to more accessible chromatin and increased gene expression); Non-histone protein acetylation enhancement (inhibitors affect acetylation of transcription factors, signaling proteins, etc.)