HDAC

Histone deacetylases (HDACs) remove acetyl groups from lysine residues on histone and non-histone proteins, thereby regulating chromatin acetylation, gene transcription, and protein function^[1]. Mechanistically, HDAC activity works opposite to histone acetyltransferases and controls chromatin conformation, with HDAC1/2 complexes also regulating histone crotonylation in vivo^[2]. In disease research, altered HDAC expression or function is linked to cancer, neurological diseases, and immune disorders, making HDAC enzymes practical targets for cellular, animal, and translational models^[3]. Compared with related isoforms, HDAC3 is distinguished by its dependence on SMRT/N-CoR corepressor complexes for enzymatic activity, whereas class II HDAC-associated deacetylase activity depends on multiprotein complexes containing HDAC3 and SMRT/N-CoR^[4][5]. HDAC6 differs functionally because it localizes mainly in the cytoplasm, deacetylates α-tubulin, associates with microtubules, and regulates aggresome formation under misfolded-protein stress^[6][7][8]. For experimental applications, HDAC inhibitors provide small-molecule tools to increase acetylation, induce p21-associated cell-cycle arrest, differentiation, or apoptosis, and interrogate isoform-selective HDAC biology in disease models^[3][9][10].