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Overview
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Histones are the chief protein components of chromatin, which act as spools around which DNA winds. Covalent modification of histone proteins through acetylation and deacetylation affects chromatin structure and regulates gene expression. Histone hyperacetylation is well correlated with increased transcription, whereas hypoacetylation correlates with transcriptional repression. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from an ɛ-N-acetyl lysine amino acid on a histone, and act as transcriptional repressors of genes. Histone deacetylases have been grouped into three classes. Class I (HDAC 1, 2, 3, 8) and Class II (HDAC 4, 5, 6, 7, and 9) are zinc-containing hydrolase enzymes. Class III of deacetylases consists of the members of the sirtuin family of enzymes (Sir 1 to 7). Inhibitors of HDAC classes II and I are being studied as a treatment for cancer and neurodegenerative diseases such as Huntington’s and Alzheimer’s diseases. The Sirtuin 1 (class III) enzyme represents a target for the treatment of age-related diseases and type II diabetes.
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Overview