HDACs,histone deacetylation and gene transcription: from molecular biology to cancer therapeutics

Histone deacetylases(HDACs)and histone acetyl transferases(HATs)are two counteracting enzyme families whoseenzymatic activity controls the acetylation state of protein lysine residues,notably those contained in the N-terminalextensions of the core histones.Acetylation of histones affects gene expression through its influence on chromatin confor-mation.In addition,several non-histone proteins are regulated in their stability or biological function by the acetylationstate of specific lysine residues.HDACs intervene in a multitude of biological processes and are part of a multiproteinfamily in which each member has its specialized functions.In addition,HDAC activity is tightly controlled throughtargeted recruitment,protein-protein interactions and post-translational modifications.Control of cell cycle progression,cell survival and differentiation are among the most important roles of these enzymes.Since these processes are affectedby malignant transforlnation,HDAC inhibitors were developed as antineoplastic drugs and are showing encouragingefficacy in cancer patients.