Histone Deacetylases

There are 18 Histone Deacetylase (HDAC) enzymes that are classified into two groups, the histone deacetylase family and the sirtuin family. The histone deacetylase family is divided into classes I, II and IV.

Targets | Literature | Enzyme Data

Histone Deacetylase Targets

There are 18 Histone deacetylases (HDAC) enzymes that are classified in to two families, the histone deacetylase family and the sirtuin family. The histone deacetylase family is further divided in to class I (HDACs 1/2/3 and 8), class II (HDACs 4/5/6/7/9/10) and class IV (HDAC 11). The sirtuin family are all classified as class III HDACs. HDACs catalyze acetyl group removal from lysine residues in histones and non-histone proteins, causing transcriptional repression. In general, they do not act autonomously but as components of large multiprotein complexes, such as pRb-E2F and mSin3A, that mediate important transcription regulatory pathways.

Classes I, II and IV, are closely related Zn²⁺-dependent enzymes, which are ubiquitously expressed and they can exist in the nucleus or cytosol. Their subcellular localization is affected by protein-protein interactions (for example HDAC-14.3.3 complexes are retained in the cytosol) and by the class to which they belong (class 1 HDACs are predominantly nuclear whilst class 2 HDACs shuttle between the nucleus and cytosol). HDACs have a role in cell growth arrest, differentiation and death and this has led to substantial interest in HDAC inhibitors as possible antineoplastic agents.

Histone acetylation - a key epigenetic process - is upregulated during memory formation but downregulated in numerous neurodegenerative diseases, such as Alzheimer's disease and Huntington's disease. As a result, HDAC inhibitors are also of great interest in neuroscience research.

Literature

Enzyme Data