Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl groups from the lysine residues of histones. They play a pivotal role in the regulation of gene transcription and are indispensable in numerous eukaryotic biological processes involving chromatin. Many studies have shown HDACs to be a key component in controlling cell cycle progression, cell proliferation, and differentiation. Currently, there are eighteen HDAC enzymes which have been identified in humans, and categorized into four classes: Class 1 Rpd3-like proteins (HDAC1, HDAC2, HDAC4, and HDAC8); Class II Hda1-like proteins (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10); Class III Sir2-like proteins (SIRT1-7); and the Class IV HDAC11 protein. Each of these HDACs vary in histone substrate specificity, as well as the histone amino acid they will deacetylate.
Abnormal HDACs are strongly correlated with many human maladies including cancer, neurodegenerative disorders, cardiac hypertrophy, and pulmonary diseases. Therefore, the Seto lab is devoted to obtaining a complete understanding of the functions, mechanisms of action, and regulation of HDACs. They also seek to examine the molecular mechanisms by which HDAC inhibitors alter gene expression in both normal and cancer cells. They hope that a thorough understanding of the biology of HDACs will not only provide great insight into epigenetics and gene regulation, but also aid in establishing potential diagnostic and therapeutic approaches for the treatment of diseases.