The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy

Histone deacetylases (HDACs) are potent regulators of gene expression, yet incomplete understanding of individual HDAC function coupled with the lack of selective inhibitors has impeded successful targeting of these proteins for the improvement of human health. Although all HDAC proteins contain a deacetylase domain, the 18 distinct human HDAC proteins have remarkably distinct mechanisms of action. In a misleading oversimplification, HDACs are often thought to uniformly deacetylate histones to affect global gene expression in a functionally redundant manner. Instead, findings continue to define the distinct roles of individual HDACs, highlighting the potential value of data-driven precision targeting of individual HDACs or specific subclasses of HDACs for disease therapy. Here, we will discuss this decade's advances about how the zinc-dependent HDACs, HDAC1 to HDAC11, regulate gene expression in health and disease.