The Histone Deacetylase Family

By its nature, reversible acetylation of a target implies that the acetyl group can also be removed. For every acetyltransferase that acetylates a substrate, there must be a deacetylase that does the reverse. Although prominent exceptions do exist (see below), generally speaking, HDACs are anti-HATs: they are associated with transcription repression complexes and repressive chromatin states (Fig. 6.IB). Dynamic control of gene expression is critical in biology, and shutting off transcription is as important as turning it on. Therefore HDACs have as wide a range of biological roles as HATs. Based on sequence homology, there are eighteen mammalian HDACs known. They are divided into three classes (class I, II, and III) based on the similarity of their enzymatic (HDAC) domains to the yeast prototypes Rpd3 (Class I) and Hdal (Class II) as well as their requirement for NAD+ for enzymatic activity (Class III). We will consider each of the classes in turn.

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