Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl groups from histones, resulting in the compacting of chromatin and transcriptional repression. They are classified into four main families: Classes I, II, III and IV. Class I HDACs include HDAC1, 2, 3 and 8; class IIa includes HDAC4, 5, 7 and 9; class IIb contains HDAC6 and 10; class III comprises the sirtuins 1-7; finally, class IV has only one member, HDAC11. These enzymes are found in a variety of organisms ranging from bacteria to humans.
The activity of histone deacetylases is important for proper cell proliferation and differentiation during development. For example, they play a role in embryogenesis by regulating gene expression involved in early developmental processes such as patterning and cell fate determination. In addition, they are also involved in neurogenesis, myogenesis and hematopoiesis. Furthermore, histone deacetylases have been implicated in various diseases including cancer (e.g., through their involvement in epigenetic silencing of tumor suppressor genes), neurodegenerative disorders (e.g., Huntington’s disease) and autoimmune diseases (e.g., multiple sclerosis).
The first histone deacetylase was isolated from yeast in the 1970s Since then much progress has been made in our understanding of their structure-function relationships as well as their physiological roles. Currently available drugs that target histone deacetylases are being explored for their therapeutic potential both alone and in combination with other agents for treating cancer and other diseases