Epigenetic modications of histones such as acetylation cause conformational changes in the chromatin structure, thereby regulating transcriptional activity. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are enzymes responsible for such post-translational modification of core histones. HDACs remove acetyl groups from lysine residues and are separated into four categories: Class I (HDAC1, 2, 3 & 8), Class II (HDAC4-9), Class III (SIRT 1-7) and Class IV (HDAC11). Class I, II, and IV are zinc-dependent deacetylases while Class III is NAD-dependent. HDACs have been shown to play a significant role in the development of neurodegenerative and metabolic disorders. Thus, HDAC modulators could provide viable treatment options and are currently targeted for drug discovery.
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