Controversies Surrounding the Potential Use of Histone Deacetylase Inhibitors for the Treatment of Asthma

Figure 1

Histone acetylation is regulated by the opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs catalyze the addition of the acetyl moiety of acetyl-coA to the ε-amino group of lysine residues in the core histones resulting in a more open, transcriptionally permissive, chromatin conformation. HDAC enzymes remove acetyl groups from lysine residues resulting in a more condensed chromatin conformation and transcriptional repression. Numerous nonhistone proteins are also targets for deacetylation by HDACs. These include proteins involved in gene transcription (e.g., p53), DNA repair (e.g., Ku70), chaperones (e.g., HSP90) and cell motility (e.g., α-tubulin).