HDAC Inhibitors and HAT Activators – Different Activity, Same Outcome

Histone acetyltransferases (HATs) are a group of enzymes that acetylate lysine residues in histones, which are bound to DNA in all eukaryotes to form a complex and well organized structure called chromatin. HATs play an important role in regulating the chromatin organization and accessibility of the DNA to the transcriptional machinery by altering the acetylation status of histones in particular gene loci by chromatin remodeling. Histone acetylation marks active gene transcription while lack of acetylation marks gene repression. The –acetyl moieties are removed from the histones by Histone deacetylases (HDACs). Thus HATs and HDACs play a dynamic role in switching a gene ON and OFF. Dysfunction and deregulation of these enzymes leads to aberrant expression of genes thereby affecting the cellular phenotype, resulting in diseases like cancer and neurodegenerative disorders [1,2]. Several proteins including transcription factors also undergo dynamic acetylation and deacetylation processesthat affects protein-protein interactions, protein-DNA interactions and cellular localization thereby changing the physiology of the cell. Thus in several disease models HATs and HDACs are attractive targets for manipulating the gene expression by altering their activity by small molecule modulators.