Histone deacetylases, transcriptional control, and cancer

A key event in the regulation of eukaryotic gene expression is the posttran slational modification of nucleosomal histones, which converts regions of c hromosomes into transcriptionally active or inactive chromatin. The most we ll studied post-translational modification of histones is the acetylation o f epsilon-amino groups on conserved lysine residues in the histones' amino- terminal tail domains. Significant advances have been made in the past few years toward the identification of histone acetyltransferases and histone d eacetylases. Currently, there are over a dozen cloned histone acetyltransfe rases and at least eight cloned human histone deacetylases. Interestingly, many histone deacetylases can function as transcriptional corepressors and, often, they are present in multi-subunit complexes. More intriguing, at le ast some histone deacetylases are associated with chromatin-remodeling mach ines. In addition, several studies have pointed to the possible involvement of histone deacetylases in human cancer. The availability of the cloned hi stone deacetylase genes has provided swift progress in the understanding of the mechanisms of deacetylases, their role in transcription, and their pos sible role in health and disease. J. Cell. Physiol. 184:1-16, 2000. (C) 200 0 Wiley-Liss, Inc.