A mouse mammary tumor virus promoter element near the transcription initiation site

Transcription from the promoter of mouse mammary tumor virus is subject to both positive and negative control by cellular factors, and proviral promoter elements that mediate a basal level of transcription must in some way respond to these cellular regulatory signals. Several such elements, including a TATA box, a region containing three octamer-related sequences, and a binding site for nuclear factor 1, have been previously defined. Additional promoter mutations have allowed a fourth basal promoter element to be identified near the transcription initiation site between +2 and +10. Sequence alterations within this element affect transcription both in vivo and in vitro. Gel electrophoresis mobility shift and DNase I footprinting assays define a nuclear protein, termed initiation site-binding protein, that specifically recognizes this region of the promoter. Optimal levels of transcription from the mouse mammary tumor virus promoter require initiation site-binding protein, as demonstrated by a correlation between protein affinity and transcriptional activity and by specific inhibition of transcription in vitro by an oligonucleotide capable of titrating the protein from transcriptionally active fractions.