CHARACTERIZATION OF THE MURINE THYMIDINE KINASE-ENCODING GENE AND ANALYSIS OF TRANSCRIPTION START POINT HETEROGENEITY

We have determined the molecular organization and transcription start points (tsp) for the murine gene (TK) encoding thymidine kinase. The exon/intron structure and sequences present at the splice junctions of the mammalian TK genes have been highly conserved; however, the promoter sequences of these genes have diverged widely. Both the human and Chinese hamster TK promoter regions contain CCAAT and TATA consensus motifs, whereas the mouse promoter has neither element. This difference between species is reflected in that, unlike the hamster and human TK genes, transcription initiates from numerous specific tsp within a 100-bp region in the mouse TK gene. The complex pattern of tsp seen in the endogenous gene was not maintained in transfected cell lines containing TK promoter=beta-globin (HBB) fusions. Transcription from the murine TK=HBB fusion genes initiated from a small number of tsp that were clustered downstream from the ATG in hybrids containing TK coding sequences, and in the HBB 5' UTR in hybrids that did not. Few or no specific tsp were detected from the upstream sites used in the endogenous mouse TK gene.