Chromatin domains and nuclear compartments: establishing sites of gene expression in eukaryotic nuclei

Establishing sites of transcription in the nuclei of higher eukaryotic cells is a very complex process. Before transcription can begin, a series of transcription factors must associate with their recognition motifs, within promoters and more remote activating sequences. Once bound, these factors and associated proteins are believed to form a complex that positions the RNA polymerase holoenzyme so that transcription can commence. As a consequence, active genes assume a specialized chromatin state across regions that define functional domains. Global nuclear architecture appears to stabilize these active domains by providing local environments dedicated to gene expression. As the spatial organization of these sites is unaffected by the removal of most chromatin they must be associated with a structural network. This nucleoskeleton, the associated transcription 'factories' and chromatin loops that arise as DNA binds proteins within factories now appear to be fundamental features of nuclear structure in higher eukaryotes. I argue that concentrating proteins needed to perform different steps of RNA synthesis within specialized nuclear compartments will be important in orchestrating events required for efficient gene expression.