G1-S Regulatory Promoter Elements and their Interacting Transcription Factors

Modulation of S-phase linked transcription in cell cycle regulated genes can be attributed to cis regulatory elements found in their promoters (Naeve et al., 1991; Johnson, 1992). Characterization of the factors that act through these elements provides the basic principle for understanding the mechanism that regulates the periodic transcription changes of cell cycle regulated genes. The G1/S border is a key regulatory point in the cell cycle that directs the fate of a cell to duplicate itself. As such, the events leading to this point must provide the appropriate signals for the replication machinery to be duplicated in anticipation for the division of a daughter cell. The signals for the transcriptional regulation of the replication-dependent genes are generated by what are proving to be multi-functional transcription factors. Our laboratory is interested in the target regulatory elements these factors act on in cell cycle regulated genes as studied in growth stimulated cells. The hamster histone H3.2 and human thymidine kinase genes contain characterized promoter elements that are known to be involved in their replication-dependent transcriptional increase. Current work is focusing on the identification and characterization of the factors that interact with these elements and to understand how they elicit their regulation.