IDENTIFICATION OF A 70-BASE-PAIR CELL-CYCLE REGULATORY UNIT WITHIN THE PROMOTER OF THE HUMAN THYMIDINE KINASE GENE AND ITS INTERACTION WITH CELLULAR FACTORS

The promoter of the human thymidine kinase gene contains cis-regulatory elements responsible for its cell-cycle-regulated expression. We report here that a 70-bp region between -133 and -64 is sufficient to confer cell cycle regulation on a heterologous promoter. The 20-bp region between -64 and -83, which contains an inverted CCAAT motif, is important for transcriptional stimulation of this functional unit. The sequence of this CCAAT motif is nearly identical to the consensus sequence for the transcriptional factor CP1. We also examined the specificity and binding activities of cellular factors interacting with the 70-bp fragment. We showed that the cellular factors binding to the 70-bp region are similar during the G1, S, and G2 phases, suggesting that the cell cycle regulatory activity observed must involve processes other than factor binding to the DNA.