Histone deacetylases, the erasers of the code

Abstract

The acetylation of the N-terminal tail domains of core histones provides a rich potential source of epigenetic information. Acetylation involves the addition of an acetyl group to a lysine residue by the action of the histone/lysine acetyltransferase enzymes (HATs/KATs). As acetylation of histone tails is a reversible process, the acetyl group can be removed by histone deacetylases (HDACs). In this chapter, we will focus on the 18 human HDACs, as essential contributors to active transcription, well known as ?erasers? of the histone code. HDACs are classified in four classes (I?IV) according to homology to yeast proteins and sequence similarity. Their catalytic activity depends on essential and conserved motifs and residues. Here, we also discuss the developmental and physiological functions of HDACs that are revealed by gene deletions in mice. In addition, HDACs execute their deacetylation activity on both histone and non-histone substrates. The interaction between deacetylases and different chromatin modifiers impacts on gene expression. Overall, this chapter will improve the knowledge of structure, functions, and mechanisms of HDACs action, and this will lead us to understand the impact of this family on human health and disease.