Complex Transcriptional Initiation Pattern of the Thymidylate Synthase Promoter in Mouse Tissues

Thymidylate synthase (TS) is an essential enzyme that must be expressed in all proliferating cells. The mouse TS promoter lacks a TATA box and an initiator element and initiates transcription over a broad region in cultured fibroblasts. The goal of this study was to determine if expression of the TS gene in a variety of cells and tissues involves the use of alternative promoters or different patterns of transcriptional initiation sites. The amount of TS mRNA and the pattern of initiation sites were determined using S1 nuclease protection assays. We found that even though the amount of TS mRNA varied over a wide range, reflecting differences in cell proliferation rates, the pattern of initiation sites was nearly identical in all of the cell lines and tissues that were examined. Therefore transcription of the TS gene is directed by a single promoter that is capable of being expressed in a wide variety of cellular environments.