Chromatin remodeling and transcriptional regulation

Extensive studies in the past few years have begun to demonstrate that chro mosome structure plays a critical role in transcriptional regulation. Two h ighly conserved mechanisms for altering chromosome structure have been iden tified: 1) post-translational modification of histones and 2) adenosine tri phosphate (ATP)-dependent chromosome remodeling. Acetylation of histone lys ine residues has been known for three decades to be associated with transcr iptional activation. Recent discoveries, however, show that a number of tra nscriptional regulators are histone acetylases or histone deacetylases. Spe cific DNA-binding transcription factors recruit histone acetylases and deac etylases to promoters to activate or repress transcription, These results s trongly support the notion that histone acetylation and deacetylation play an important role in transcriptional regulation. Recent findings have also provided insight into the molecular mechanisms by which ATP-dependent chrom osome-remodeling activities participate in transcriptional regulation. Furt hermore, some ATP-dependent chromosome-remodeling activities have been show n to complex with histone deacetylases. In the complexes studied to date, t he ATP-dependent chromosome-remodeling activity enhances the histone deacet ylase activity. Therefore, the two mechanisms appear to work in concert to achieve precise control of transcription. Disruption of chromosome remodeli ng has been linked to a number of diseases, and a complete understanding of the complex chromosome-remodeling machinery may lead to the development of new therapies.