Transcription from TATA-less promoters: dihydrofolate reductase as a model.

The promoters of many of the genes encoding the so-called "housekeeping" enzymes, oncogenes, growth factors and their receptors, and transcription factors, do not contain a canonical TATA box, which is known to direct transcription initiation. The mechanisms through which TATA-less promoters are regulated, and their transcription start sites selected, have begun to yield to investigation. Using the dihydrofolate reductase (DHFR) gene as a model, recent work on this group of genes has been reviewed. Control of transcription initiation and the role of "initiator" sequences, as well as their binding factors, in particular YY1 and E2F, are addressed. In the DHFR gene, neither the E2F site at the major initiation region nor the upstream Sp1 sites can alone produce wild-type initiation, despite the fact that each of these sites has certain properties of initiators. Many TATA-less genes are growth regulated, that is, transcription is increased in response to stimulation of cell proliferation. Although both Sp1 and E2F have been implicated in growth regulation, our recent studies suggest that Sp1 sites alone can confer a growth-dependent increase in transcription in the late G1 and early S phases of the cell cycle. The regulatory role of E2F, which binds to many TATA-less promoters and mediates viral stimulation of transcription, is also reviewed.