Histone Acetylation Mechanism

Enzyme: Histone Acetyltransferases (HATs) (Fig. 1)[17]

The lysine residue on the histone tail is associated with gene activation. Once acetylated, the positive charge on lysine residue is neutralized, resulting in reduced affinity between histone and DNA. Histone acetylation opens up access to DNA for transcription factors and polymerases, and therefore enhancing transcription [11].

Histone acetylation consists of the following steps (Fig. 2)[11].

1. A  glutamate residue on HATs acts as a general base and activates the lysine ε-amino group by deprotonation. Nucleophilic attack on the carbonyl group of acetyl CoA.
2. A tetrahedral intermediate forms, and then collapses with the loss of coenzyme A (CoASH) through elimination. The lysine residue on the tail of histone is acetylated and loses its positive charge [16].