Lysine acetylation refers to the transfer of the acetyl moiety from acetyl coenzyme A to the ε-amino group of a lysine residue. Specific lysine residues, enriched at the N-terminal tails of core histones H2A, H2B, H3, and H4, are subject to this modification. Each core histone contains multiple lysine residues for acetylation, and the functional impact is site specific. Due to its polymeric nature, chromatin is a unique substrate in that locus-specific histone acetylation dictates its impact on expression of genes. This modification is reversible, and the forward reaction is catalyzed by histone acetyltransferases (HATs). Due to historical reasons, these enzymes have been known as HATs, even though they also target many nonhistone proteins. Since the initial molecular identification of HATs in the mid-1990s, a dozen human proteins have been well demonstrated to possess intrinsic HAT activities. This chapter provides an overview of histone acetylation and the well-characterized yeast and metazoan HATs, especially their molecular interaction with noncatalytic subunits within multiprotein complexes and their important roles in regulating animal development. Also included in this chapter is a survey about direct genetic links of human HATs to cancer, developmental disorders, neurodegenerative diseases, and other pathological conditions.
