Chromatin Structure and DNA Replication: Implications for Transcriptional Activity

The period in the cell cycle when the genome is replicated (S phase) is crucially important for the establishment and maintenance of programs of differential gene activity. Not only must DNA be replicated, but the chromosome itself must be duplicated. The majority of genes in the proliferating cell of a defined type retain the same states of transcriptional activity through cell division. This requires the duplication of the precise nucleoprotein complexes directing gene transcription or repression on the nascent DNA templates. The maintenance of these specific regulatory complexes through replication reflects the commitment of a defined cell type or line to a particular state of determination. Preexisting chromosomal structures are transiently disrupted by transit through the replication elongation complex. Most of these structures are faithfully reassembled following replication through mechanisms discussed in this chapter. However, the transient disruption of these structures also offers a window of opportunity for modifying regulatory nucleoprotein complexes. These alterations can either activate genes through the disruption of repressed states, or direct the repression of previously active genes. Thus, cell division offers a molecular mechanism to redirect the commitment of a cell toward a particular determined state. A consideration of the processes occurring at the eukaryotic replication fork suggests how this important development process might be accomplished.