Histone deacetylase enzyme family (HDAC)

The **histone deacetylase enzyme family** comprises several classes of enzymes (HDAC1-11 and sirtuins/SIRT1-7) that remove acetyl groups from ε-N-acetyl lysine residues on histones and numerous non-histone proteins[1][2][3][5]. This reversible modification regulates chromatin structure and gene expression: acetylated histones relax chromatin, promoting transcription, while deacetylated histones condense chromatin, silencing genes[3][4]. HDACs are grouped into four classes based on structure and cofactor dependency: - **Class I (HDAC1, 2, 3, 8):** Nuclear, zinc-dependent, broad deacetylation activity. - **Class II (HDAC4, 5, 6, 7, 9, 10):** Can shuttle between nucleus and cytoplasm, subdivided into IIa and IIb. - **Class III (Sirtuins/SIRT1-7):** NAD+-dependent, structurally distinct, involved in metabolic regulation[2]. - **Class IV (HDAC11):** Shortest protein, unique activity[2]. HDACs influence fundamental cellular processes, including transcriptional repression, cell cycle regulation, apoptosis, and DNA repair[3][4]. Dysregulation of HDAC activity contributes to diseases such as cancer and neurological disorders, making them major therapeutic targets[5]. Several HDAC inhibitors (HDACis) are approved for cancer treatment and are under investigation for additional indications. Safety concerns with HDAC inhibitors include hematological, cardiac, gastrointestinal, and neurological toxicities[2][5]. HDAC activity and expression levels are used as biomarkers for patient selection and therapeutic monitoring in oncology and other diseases[2][3].

Other names

HDACsHistone deacetylaseLysine deacetylase (KDAC)

HDAC inhibitors block deacetylase activity, leading to increased acetylation of histones and non-histone proteins, resulting in chromatin relaxation, increased gene expression, and promotion of apoptosis in cancer cells.