Histone acetylation modulation by small molecules: a chemical approach.

Histone acetyltransferases (HATs) are enzymes able to acetylate lysine side chains of histones. They play essential roles in normal cell function as well as in pathogenesis of a broad set of diseases, including multiple cancers, HIV, diabetes mellitus, and neurodegenerative disorders. Moreover, several HATs are able to acetylate various non-histone protein substrates e.g. transcription factors, enzymes involved in glycolysis, fatty acid and glycogen metabolism, the tricarboxylic acid and urea cycles, suggesting that lysine acetylation represents an important regulatory mechanism similar to protein phosphorylation. Small molecule inhibitors of histone acetyltransferases have been developed in the last years and proved to be powerful tools to provide new insights into the mechanisms and the role of protein acetylation in gene regulation. This article highlights recent advances in the development of small molecule modulators of histone acetyltransferases.