Transcriptional regulation in eukaryotes occurs within a chromatin setting, and is strongly influenced by the post-translational modification of histones, the building blocks of chromatin, such as methylation, phosphorylation and acetylation. Acetylation is probably the best understood of these modifications: hyperacetylation leads to an increase in the expression of particular genes, and hypoacetylation has the opposite effect. Many studies have identified several large, multisubunit enzyme complexes that are responsible for the targeted deacetylation of histones. The aim of this review is to give a comprehensive overview of the structure, function and tissue distribution of members of the classical histone deacetylase (HDAC) family, in order to gain insight into the regulation of gene expression through HDAC activity. SAGE (serial analysis of gene expression) data show that HDACs are generally expressed in almost all tissues investigated. Surprisingly, no major differences were observed between the expression pattern in normal and malignant tissues. However, significant variation in HDAC expression was observed within tissue types. HDAC inhibitors have been shown to induce specific changes in gene expression and to influence a variety of other processes, including growth arrest, differentiation, cytotoxicity and induction of apoptosis. This challenging field has generated many fascinating results which will ultimately lead to a better understanding of the mechanism of gene transcription as a whole.
Abbreviations used: CaMK, Ca2+/calmodulin-dependent kinase; CtBP, C-terminal binding protein; HDAC, histone deacetylase; HDACi, histone deacetylase inhibitor(s); HDRP, HDAC-related protein; MEF2, myocyte enhancer factor 2; N-CoR, nuclear receptor co-repressor; NES, nuclear export signal; NLS, nuclear localization signal; NuRD, nucleosome remodelling histone deacetylase; Rb, retinoblastoma protein; RbAp46/48, Rb-associated protein 46/48; SAGE, serial analysis of gene expression; SMRT, silencing mediator for retinoic acid and thyroid hormone receptors; TSA, trichostatin A; YY1, Yin and Yang 1.