Initiation of DNA replication at the rat aldolase Blocus

摘要

In higher eukaryotes, DNA replication initiates at multiple sites on each chromosome. Positioning and firing of the replication origins are not fixed, but different and selected origins may initiate at different times in a single cell cycle of particular cells through a range of complex mechanisms controlling, for example, cell differentiation. The origin region at the rat aldolase B locus (ori A1) has been found to encompass the promoter which governs liver-specific transcription. Ori A1 is, thus, thought to be a suitable target in investigating causal relationships among those under control of cell differentiation, i.e., firing or silencing of the origin, cell type-specific regulation of transcription, and positioning of nearby origins. In this article, we summarize our approach to elucidate such relationships. We describe sequence-dependent replication from ori A1, overlapping of essential regions required for replication and transcription, cell cycle-regulated binding of factors to the essential region, and then chromosomal state of the ori A1 region in the nucleus.